JP2018164452A

JP2018164452A - Method for determining susceptibility to freckles

Info

Publication number: JP2018164452A
Application number: JP2018049787A
Authority: JP
Inventors: 良子森野; Ryoko Morino
Original assignee: Evergene Co Ltd
Current assignee: Evergene Co Ltd
Priority date: 2017-03-28
Filing date: 2018-03-16
Publication date: 2018-10-25

Abstract

PROBLEM TO BE SOLVED: To provide a method for comprehensively grasping susceptibility of subjects to freckles.SOLUTION: The present invention provides a method for comprehensively grasping susceptibility of subjects to freckles, including the step of detecting, in DNA-containing samples derived from subjects, one or more single nucleotide polymorphisms selected from the groups shown in Tables 1-7 registered in the National Center for Biotechnology Information (NCBI) SNP database and/or single nucleotide polymorphisms, insertion type polymorphisms, deficiency type polymorphisms, or base repeating polymorphisms in linkage disequilibrium to the single nucleotide polymorphisms.SELECTED DRAWING: None

Description

本発明は、遺伝子多型を検出する工程を含む被験者のソバカスになり易さを判定する方法に関する。さらに詳しくは、被験者由来のDNA含有試料において特定の遺伝子多型を検出する工程を含む被験者のソバカスになり易さを判定する方法に関する。 The present invention relates to a method for determining the likelihood of becoming a test subject's buckwheat that includes a step of detecting a genetic polymorphism. More specifically, the present invention relates to a method for determining the likelihood of becoming a test subject's buckwheat that includes a step of detecting a specific gene polymorphism in a subject-containing DNA-containing sample.

皮膚が紫外線にさらされること等により、メラノサイトがメラニン色素を過剰に生成することによってシミやソバカスとなる。肌質はヒトによって異なるため、近年ではそれぞれのヒトに適した化粧品の提供等を目的としてシミやソバカスになり易さを判別する方法が検討されている。 When the skin is exposed to ultraviolet rays or the like, melanocytes produce stains and freckles due to excessive production of melanin pigment. Since the skin quality varies from person to person, in recent years, methods for determining the likelihood of becoming spots and freckles have been studied for the purpose of providing cosmetics suitable for each person.

例えば、特許文献１では、ヒトメラノサイト刺激ホルモン１受容体(MC1R)のアミノ酸配列において、特定の箇所のアミノ酸の変異が存在する場合に、皮膚におけるシミもしくはソバカス又は毛髪における茶色の髪の発生確率が高いと鑑別する方法が開示されている。また、特許文献２では、被験者から単離した生体試料について、ASIP遺伝子、MMP1遺伝子、Filaggrin遺伝子及びSPINK5遺伝子の遺伝子型に基づき、被験者がシミ（ソバカス）を生じるリスクが高い肌質であるか否か等を判定することが可能であると開示されている。しかし、これらに開示されている方法では特定の遺伝子の特定のアミノ酸配列や遺伝型のみを対象とするものであり、シミやソバカスになり易さを網羅的に把握できる方法は提供されていなかった。 For example, in Patent Document 1, when there is an amino acid mutation at a specific position in the amino acid sequence of human melanocyte stimulating hormone 1 receptor (MC1R), the probability of occurrence of spots or freckles in skin or brown hair in hair is known. A method of discriminating as high is disclosed. Further, in Patent Document 2, whether or not a biological sample isolated from a subject has a high skin risk that causes the subject to develop spots (sobacus) based on the genotypes of the ASIP gene, MMP1 gene, Filaggrin gene, and SPINK5 gene. It is disclosed that it can be determined. However, the methods disclosed in these methods are intended only for specific amino acid sequences and genotypes of specific genes, and no method has been provided that can comprehensively grasp the likelihood of becoming spots or freckles. .

特許第4817666号公報Japanese Patent No. 4817666 特開2013-226096号公報JP 2013-226096

それぞれの被験者について、ソバカスになり易さを網羅的に把握できる方法の提供を課題とする。 For each subject, the problem is to provide a method that can comprehensively grasp the likelihood of becoming a buckwheat.

本発明者らは、前記課題を解決するために鋭意研究を行い、複数のヒトのソバカスになり易さと遺伝型との関連を調べた結果、米国バイオテクノロジー情報センター（NCBI）SNPデータベースに登録されている表１〜７に示される群から選択される一以上の一塩基多型及び／或いは該一塩基多型と連鎖不平衡にある一塩基多型、挿入型多型、欠失型多型、又は塩基繰り返し多型を対象として解析することにより、網羅的に被験者のソバカスになり易さを判定することができることを見出し、本発明を完成するに至った。 The present inventors conducted intensive research to solve the above-mentioned problems, and as a result of investigating the relationship between the likelihood of becoming multiple human buckwheat and the genotype, they were registered in the National Center for Biotechnology Information (NCBI) SNP database. One or more single nucleotide polymorphisms selected from the group shown in Tables 1 to 7 and / or single nucleotide polymorphisms, insertion polymorphisms, deletion polymorphisms in linkage disequilibrium with the single nucleotide polymorphisms Or, it has been found that it is possible to comprehensively determine the likelihood of becoming a test subject's buckwheat by analyzing base polymorphisms, and the present invention has been completed.

さらに本発明者らは、これらの遺伝子多型を含む遺伝子か又は該遺伝子の近傍の遺伝子としてPPARGC1B遺伝子、BNC2遺伝子、又はHSPA12A遺伝子又はを見出し、これらの遺伝子の発現を制御することや、合成されたタンパク質の作用を抑制することが、ソバカスの予防又は治療に有用であることを見出した。 Furthermore, the present inventors have found PPARGC1B gene, BNC2 gene, or HSPA12A gene as a gene containing these gene polymorphisms or a gene in the vicinity of the gene, and controlling the expression of these genes or synthesized them. It was found that suppressing the action of the protein is useful for the prevention or treatment of buckwheat.

すなわち、本発明は次の（１）〜（８）の被験者のソバカスになり易さを判定する方法等に関する。
（１）被験者由来のDNA含有試料において遺伝子多型を検出する工程を含む被験者のソバカスになり易さを判定する方法であって、検出する遺伝子多型が米国バイオテクノロジー情報センター（NCBI）SNPデータベースに登録されている表１〜７に示される群から選択される一以上の一塩基多型及び／或いは該一塩基多型と連鎖不平衡にある一塩基多型、挿入型多型、欠失型多型、又は塩基繰り返し多型である、被験者のソバカスになり易さを判定する方法。
（２）被験者由来のDNA含有試料において遺伝子多型を検出する工程を含む被験者のソバカスになり易さを判定する方法であって、検出の対象となる一塩基多型がrs75548653、rs79694606、rs79489540、rs4235745、rs78814834、rs4705384、rs67393352、rs17110447、rs77655035、rs251468、rs80069564、rs109075、rs109076、rs251467、rs251466、rs17110463、rs251465、rs251464、rs251463、rs251462、rs4705385、rs109077、rs112183859、rs251460、rs76390604、rs17600568、rs10491360、rs251459、rs79435714、rs32589、rs32588、rs32587、rs32586、rs2003602、rs32585、rs28282、rs17653577、rs32584、rs32583、rs17110586、rs32581、rs45560442、rs76994147、rs45520937、rs45588534、rs45543631、rs75739000、rs6579761、rs1549186、rs1549187、rs1549188、rs26122、rs1107344、rs2341294、rs888853、rs7712296、rs17653703、rs10756813、rs10756814、rs76211545、rs74645810、rs76233908、rs12376135、rs10810635、rs16935073、rs10962601、rs10962609、rs4455968、rs4523356、rs12351269、rs10121347、rs10122901、rs2921966、rs3010462、rs3010463、rs1900500、rs2921967、rs2921968、rs2907238、rs2907237、rs2921969、rs7902159、rs7902262、rs3010464、rs1076369、rs1076368、rs1076367、rs740595、rs733216、rs2240711、rs2240710、rs2921971、rs12263233、rs3010467、rs12265205、rs2907231、rs3010468、rs2921972、rs3010469、rs3010470、rs12259725、rs12259865、rs71500866、rs12259866、rs12259830、rs12259842、rs12245201、rs12782444、rs3010471、rs2921973、rs3010475、rs3010476、rs3010477、rs2907230、rs3010478、rs3010479、rs3010480、rs3010481、rs2901119、rs2420327、rs3010484、rs2907229、rs2420328、rs2420329、rs2901120、rs3010488、rs3010489、rs2240709、rs2240708、rs2907241、rs2921974、rs12245621、rs2921975、rs2921976、rs3010491、rs77204400、rs1638429、rs758368、rs4752110、rs7070575、rs12146158、rs10444110、rs11198112、rs10444039、rs17096846、rs1925257、rs1925258、rs55927713、rs35563099、rs7098111、rs7074192、rs12773211、rs555269109、rs532411111、rs4994045、rs10886144、rs34878973、rs10886148、rs4752116、rs12241016、rs11198128、rs10787798、rs10749251、rs6585463、rs1925262、rs4752117、rs10749252、rs7085292、rs4431946、rs4752118、rs4752119、rs10749253、rs4752120、rs4751641、rs10787799、rs10886150、rs11198135、rs10886151、rs1925264、rs4752122、rs11498896、rs199983705、rs11198141、rs2094020、rs10787800、rs7098136、rs12250372、rs7916406、rs61866017、rs12103642、rs8066617、rs12942131、rs10515135、rs8078098、rs916815、rs8076498、rs59521320、rs72828937、rs62060342、rs62060343、rs1016984、rs1016985、rs1016986、rs1016987、rs17220593、rs17821090、rs4794701、rs4794702、rs8064252、rs17220607、rs8081915、rs4794703、rs4452017、rs4284702、rs8067946、rs34773938、rs17220621、rs35479111、rs62060346、rs62060347、rs62060348、rs17833789、rs9907841、rs62060349、rs11079281、rs17821126、rs80243896及びrs59704173からなる群から選択される一以上の一塩基多型及び／又は該一塩基多型と連鎖不平衡にある一塩基多型である、上記（１）に記載の方法。
（３）rs75548653のアレルCを保有する遺伝型、rs79694606のアレルGを保有する遺伝型、rs79489540のアレルCを保有する遺伝型、rs4235745のアレルCを保有する遺伝型、rs78814834のアレルCを保有する遺伝型、rs4705384のアレルTを保有する遺伝型、rs67393352のアレルGを保有する遺伝型、rs17110447のアレルAを保有する遺伝型、rs77655035のアレルCを保有する遺伝型、rs251468のアレルCを保有する遺伝型、rs80069564のアレルGを保有する遺伝型、rs109075のアレルTを保有する遺伝型、rs109076のアレルTを保有する遺伝型、rs251467のアレルTを保有する遺伝型、rs251466のアレルCを保有する遺伝型、rs17110463のアレルCを保有する遺伝型、rs251465のアレルAを保有する遺伝型、rs251464のアレルGを保有する遺伝型、rs251463のアレルGを保有する遺伝型、rs251462のアレルAを保有する遺伝型、rs4705385のアレルCを保有する遺伝型、rs109077のアレルTを保有する遺伝型、rs112183859のアレルAを保有する遺伝型、rs251460のアレルTを保有する遺伝型、rs76390604のアレルTを保有する遺伝型、rs17600568のアレルCを保有する遺伝型、rs10491360のアレルTを保有する遺伝型、rs251459のアレルGを保有する遺伝型、rs79435714のアレルCを保有する遺伝型、rs32589のアレルGを保有する遺伝型、rs32588のアレルTを保有する遺伝型、rs32587のアレルTを保有する遺伝型、rs32586のアレルAを保有する遺伝型、rs2003602のアレルGを保有する遺伝型、rs32585のアレルAを保有する遺伝型、rs28282のアレルCを保有する遺伝型、rs17653577のアレルAを保有する遺伝型、rs32584のアレルAを保有する遺伝型、rs32583のアレルCを保有する遺伝型、rs17110586のアレルCを保有する遺伝型、rs32581のアレルGを保有する遺伝型、rs45560442のアレルGを保有する遺伝型、rs76994147のアレルGを保有する遺伝型、rs45520937のアレルGを保有する遺伝型、rs45588534のアレルCを保有する遺伝型、rs45543631のアレルCを保有する遺伝型、rs75739000のアレルGを保有する遺伝型、rs6579761のアレルGを保有する遺伝型、rs1549186のアレルTを保有する遺伝型、rs1549187のアレルCを保有する遺伝型、rs1549188のアレルAを保有する遺伝型、rs26122のアレルCを保有する遺伝型、rs1107344のアレルGを保有する遺伝型、rs2341294のアレルGを保有する遺伝型、rs888853のアレルAを保有する遺伝型、rs7712296のアレルCを保有する遺伝型、rs17653703のアレルCを保有する遺伝型、rs10756813のアレルCを保有する遺伝型、rs10756814のアレルAを保有する遺伝型、rs76211545のアレルGを保有する遺伝型、rs74645810のアレルTを保有する遺伝型、rs76233908のアレルAを保有する遺伝型、rs12376135のアレルAを保有する遺伝型、rs10810635のアレルCを保有する遺伝型、rs16935073のアレルCを保有する遺伝型、rs10962601のアレルGを保有する遺伝型、rs10962609のアレルCを保有する遺伝型、rs4455968のアレルTを保有する遺伝型、rs4523356のアレルAを保有する遺伝型、rs12351269のアレルCを保有する遺伝型、rs10121347のアレルCを保有する遺伝型、rs10122901のアレルGを保有する遺伝型、rs2921966のアレルTを保有する遺伝型、rs3010462のアレルAを保有する遺伝型、rs3010463のアレルAを保有する遺伝型、rs1900500のアレルTを保有する遺伝型、rs2921967のアレルGを保有する遺伝型、rs2921968のアレルAを保有する遺伝型、rs2907238のアレルAを保有する遺伝型、rs2907237のアレルCを保有する遺伝型、rs2921969のアレルTを保有する遺伝型、rs7902159のアレルGを保有する遺伝型、rs7902262のアレルTを保有する遺伝型、rs3010464のアレルAを保有する遺伝型、rs1076369のアレルAを保有する遺伝型、rs1076368のアレルTを保有する遺伝型、rs1076367のアレルGを保有する遺伝型、rs740595のアレルCを保有する遺伝型、rs733216のアレルGを保有する遺伝型、rs2240711のアレルTを保有する遺伝型、rs2240710のアレルGを保有する遺伝型、rs2921971のアレルTを保有する遺伝型、rs12263233のアレルCを保有する遺伝型、rs3010467のアレルCを保有する遺伝型、rs12265205のアレルCを保有する遺伝型、rs2907231のアレルCを保有する遺伝型、rs3010468のアレルGを保有する遺伝型、rs2921972のアレルAを保有する遺伝型、rs3010469のアレルCを保有する遺伝型、rs3010470のアレルCを保有する遺伝型、rs12259725のアレルTを保有する遺伝型、rs12259865のアレルAを保有する遺伝型、rs71500866のアレルAを保有する遺伝型、rs12259866のアレルAを保有する遺伝型、rs12259830のアレルTを保有する遺伝型、rs12259842のアレルTを保有する遺伝型、rs12245201のアレルGを保有する遺伝型、rs12782444のアレルTを保有する遺伝型、rs3010471のアレルCを保有する遺伝型、rs2921973のアレルTを保有する遺伝型、rs3010475のアレルGを保有する遺伝型、rs3010476のアレルAを保有する遺伝型、rs3010477のアレルGを保有する遺伝型、rs2907230のアレルTを保有する遺伝型、rs3010478のアレルGを保有する遺伝型、rs3010479のアレルCを保有する遺伝型、rs3010480のアレルCを保有する遺伝型、rs3010481のアレルCを保有する遺伝型、rs2901119のアレルCを保有する遺伝型、rs2420327のアレルCを保有する遺伝型、rs3010484のアレルAを保有する遺伝型、rs2907229のアレルTを保有する遺伝型、rs2420328のアレルCを保有する遺伝型、rs2420329のアレルAを保有する遺伝型、rs2901120のアレルGを保有する遺伝型、rs3010488のアレルTを保有する遺伝型、rs3010489のアレルAを保有する遺伝型、rs2240709のアレルAを保有する遺伝型、s2240708のアレルGを保有する遺伝型、rs2907241のアレルTを保有する遺伝型、rs2921974のアレルGを保有する遺伝型、rs12245621のアレルCを保有する遺伝型、rs2921975のアレルGを保有する遺伝型、rs2921976のアレルAを保有する遺伝型、rs3010491のアレルTを保有する遺伝型、rs77204400のアレルGを保有する遺伝型、rs1638429のアレルTを保有する遺伝型、rs758368のアレルAを保有する遺伝型、rs4752110のアレルTを保有する遺伝型、rs7070575のアレルCを保有する遺伝型、rs12146158のアレルCを保有する遺伝型、rs10444110のアレルTを保有する遺伝型、rs11198112のアレルCを保有する遺伝型、rs10444039のアレルCを保有する遺伝型、rs17096846のアレルAを保有する遺伝型、rs1925257のアレルAを保有する遺伝型、rs1925258のアレルTを保有する遺伝型、rs55927713のアレルTを保有する遺伝型、rs35563099のアレルCを保有する遺伝型、rs7098111のアレルCを保有する遺伝型、rs7074192のアレルGを保有する遺伝型、rs12773211のアレルCを保有する遺伝型、rs555269109のアレルGを保有する遺伝型、rs532411111のアレルGを保有する遺伝型、rs4994045のアレルCを保有する遺伝型、rs10886144のアレルAを保有する遺伝型、rs34878973のアレルGを保有する遺伝型、rs10886148のアレルGを保有する遺伝型、rs4752116のアレルCを保有する遺伝型、rs12241016のアレルCを保有する遺伝型、rs11198128のアレルAを保有する遺伝型、rs10787798のアレルCを保有する遺伝型、rs10749251のアレルTを保有する遺伝型、rs6585463のアレルAを保有する遺伝型、rs1925262のアレルGを保有する遺伝型、rs4752117のアレルCを保有する遺伝型、rs10749252のアレルAを保有する遺伝型、rs7085292のアレルCを保有する遺伝型、rs4431946のアレルCを保有する遺伝型、rs4752118のアレルCを保有する遺伝型、rs4752119のアレルAを保有する遺伝型、rs10749253のアレルGを保有する遺伝型、rs4752120のアレルTを保有する遺伝型、rs4751641のアレルGを保有する遺伝型、rs10787799のアレルGを保有する遺伝型、rs10886150のアレルCを保有する遺伝型、rs11198135のアレルCを保有する遺伝型、rs10886151のアレルGを保有する遺伝型、rs1925264のアレルCを保有する遺伝型、rs4752122のアレルAを保有する遺伝型、rs11498896のアレルGを保有する遺伝型、rs199983705のアレルTを保有する遺伝型、rs11198141のアレルTを保有する遺伝型、rs2094020のアレルGを保有する遺伝型、rs10787800のアレルCを保有する遺伝型、rs7098136のアレルTを保有する遺伝型、rs12250372のアレルGを保有する遺伝型、rs7916406のアレルGを保有する遺伝型、rs61866017のアレルGを保有する遺伝型、rs12103642のアレルAを保有する遺伝型、rs8066617のアレルAを保有する遺伝型、rs12942131のアレルTを保有する遺伝型、rs10515135のアレルCを保有する遺伝型、rs8078098のアレルGを保有する遺伝型、rs916815のアレルCを保有する遺伝型、rs8076498のアレルTを保有する遺伝型、rs59521320のアレルCを保有する遺伝型、rs72828937のアレルCを保有する遺伝型、rs62060342のアレルCを保有する遺伝型、rs62060343のアレルGを保有する遺伝型、rs1016984のアレルTを保有する遺伝型、rs1016985のアレルTを保有する遺伝型、rs1016986のアレルGを保有する遺伝型、rs1016987のアレルCを保有する遺伝型、rs17220593のアレルAを保有する遺伝型、rs17821090のアレルCを保有する遺伝型、rs4794701のアレルGを保有する遺伝型、rs4794702のアレルCを保有する遺伝型、rs8064252のアレルTを保有する遺伝型、rs17220607のアレルTを保有する遺伝型、rs8081915のアレルGを保有する遺伝型、rs4794703のアレルGを保有する遺伝型、rs4452017のアレルTを保有する遺伝型、rs4284702のアレルAを保有する遺伝型、rs8067946のアレルAを保有する遺伝型、rs34773938のアレルGを保有する遺伝型、rs17220621のアレルGを保有する遺伝型、rs35479111のアレルGを保有する遺伝型、rs62060346のアレルCを保有する遺伝型、rs62060347のアレルTを保有する遺伝型、rs62060348のアレルGを保有する遺伝型、rs17833789のアレルCを保有する遺伝型、rs9907841のアレルGを保有する遺伝型、rs62060349のアレルTを保有する遺伝型、rs11079281のアレルTを保有する遺伝型、rs17821126のアレルGを保有する遺伝型、rs80243896のアレルCを保有する遺伝型、又は、rs59704173のアレルAを保有する遺伝型のいずれか１以上の遺伝型を示す被験者はソバカスになり易いと判定する工程を含む、上記（２）に記載の方法。
（４）被験者由来のDNA含有試料において遺伝型を検出する工程を含む被験者のソバカスになり易さを判定する方法であって、検出の対象となる挿入型多型、欠失型多型、又は塩基繰り返し多型がrs140364236、rs77002482、rs5872148、rs143978112、rs67920508、rs11413212、rs67892375、rs5788185、rs36103789、rs35271333、rs34828951、rs10647236、rs148896299、rs11436341、rs5821164、rs112409672、rs111581498、rs145273475、rs530322916、rs200262366及びrs548590979からなる群から選択される一以上の挿入型多型、欠失型多型、又は塩基繰り返し多型である、上記（１）に記載の方法。
（５）rs140364236のアレルATAAGGを保有する遺伝子型、rs77002482のアレルCAAを保有する遺伝子型、rs5872148のアレルTを保有する遺伝子型、rs143978112のアレルTを保有する遺伝子型、rs67920508のアレルCを保有する遺伝子型、rs11413212のアレルATを保有する遺伝子型、rs67892375のアレルAを保有する遺伝子型、rs5788185のアレルATを保有する遺伝子型、rs36103789のアレルGAを保有する遺伝子型、rs35271333のアレルTを保有する遺伝子型、rs34828951のアレルAを保有する遺伝子型、rs10647236のアレルCを保有する遺伝子型、rs148896299のアレルGTTTAを保有する遺伝子型、rs11436341のアレルAを保有する遺伝子型、rs5821164のアレルCTを保有する遺伝子型、rs112409672のアレルTAを保有する遺伝子型、rs111581498のアレルACを保有する遺伝子型、rs145273475のアレルCCCAGCACTTTAGGAGGCTGAGGを保有する遺伝子型、rs530322916のアレルCを保有する遺伝子型、rs200262366のアレルCAAを保有する遺伝子型、又はrs548590979のアレルATを保有する遺伝子型のいずれか１以上の遺伝型を示す被験者はソバカスになり易いと判定する工程を含む、上記（４）に記載の方法。
（６）上記（１）〜（５）のいずれかに記載の一塩基多型及び／又は該一塩基多型と連鎖不平衡にある一塩基多型、挿入型多型、欠失型多型、又は塩基繰り返し多型を検出するためのプローブ又はプライマーとして用いることができる、被験者のソバカスになり易さの判定用ポリヌクレオチド。
（７）上記（６）に記載のポリヌクレオチドからなるプローブ及び／又はプライマーを含む、被験者のソバカスになり易さの判定用キット。
（８）PPARGC1B遺伝子、BNC2遺伝子、又はHSPA12A遺伝子の発現を制御し、又は該タンパク質の作用を抑制するソバカスの予防又は治療のための組成物。 That is, the present invention relates to the following methods (1) to (8) for determining the likelihood of becoming a test subject's buckwheat.
(1) A method for determining the likelihood of becoming a test subject's buckwheat including a step of detecting a genetic polymorphism in a DNA-containing sample derived from a subject, and the genetic polymorphism to be detected is the National Center for Biotechnology Information (NCBI) SNP database One or more single nucleotide polymorphisms selected from the groups shown in Tables 1 to 7 and / or single nucleotide polymorphisms, insertion polymorphisms, deletions in linkage disequilibrium with the single nucleotide polymorphisms A method of determining the likelihood of becoming a test subject's buckwheat, which is a polymorphism of a type or a base-repeat polymorphism.
(2) A method for determining the likelihood of becoming a subject's buckwheat comprising a step of detecting a genetic polymorphism in a DNA-containing sample derived from a subject, wherein the single nucleotide polymorphism to be detected is rs75548653, rs79694606, rs79489540, rs4235745, rs78814834, rs4705384, rs67393352, rs17110447, rs77655035, rs251468, rs80069564, rs109075, rs109076, rs251467, rs251466, rs17110463, rs251465, rs251464, rs251463, rs251462, rs4705385, rs109077, rs112183876, rs112183876, rs112183859 rs79435714, rs32589, rs32588, rs32587, rs32586, rs2003602, rs32585, rs28282, rs17653577, rs32584, rs32583, rs17110586, rs32581, rs45560442, rs76994147, rs45520937, rs45588534, rs45543631, rs75739000, rs6579761, rs11871861, rs1549186 rs2341294, rs888853, rs7712296, rs17653703, rs10756813, rs10756814, rs76211545, rs74645810, rs76233908, rs12376135, rs10810635, rs16935073, rs109 62601, rs10962609, rs4455968, rs4523356, rs12351269, rs10121347, rs10122901, rs2921966, rs3010462, rs3010463, rs1900500, rs2921967, rs2921968, rs2907238, rs2907237, rs2921969, rs7902159, rs7902262, rs3010464, rs1010 rs2240710, rs2921971, rs12263233, rs3010467, rs12265205, rs2907231, rs3010468, rs2921972, rs3010469, rs3010470, rs12259725, rs12259865, rs71500866, rs12259866, rs12259830, rs12259842, rs1228210, rs197310, rs1973 rs3010479, rs3010480, rs3010481, rs2901119, rs2420327, rs3010484, rs2907229, rs2420328, rs2420329, rs2901120, rs3010488, rs3010489, rs2240709, rs2240708, rs2907241, rs2921974, rs12245621, rs2921975, rs2921976774, 475 rs12146158, rs10444110, rs11198112, rs10444039, rs17096846, rs1925257, rs1925258, rs 55927713, rs35563099, rs7098111, rs7074192, rs12773211, rs12726911, rs555269109, rs532411111, rs4994045, rs10886144, rs34878973, rs10886148, rs4752116, rs12241016, rs11198128, rs10787798, rs10749251, rs6585463, rs1925262, rs4752117, rs10749 rs4752120, rs4751641, rs10787799, rs10886150, rs11198135, rs10886151, rs1925264, rs4752122, rs11498896, rs199983705, rs11198141, rs2094020, rs10787800, rs7098136, rs12250372, rs7916406, rs61866017, rs12103642, rs80131817 rs72828937, rs62060342, rs62060343, rs1016984, rs1016985, rs1016986, rs1016987, rs17220593, rs17821090, rs4794701, rs4794702, rs8064252, rs17220607, rs8081915, rs4794703, rs4452017, rs4284702, rs20679460, rs34773960, rs206777 rs9907841, rs62060349, rs11079281, rs17821126, rs802438 The method according to (1) above, wherein one or more single nucleotide polymorphisms selected from the group consisting of 96 and rs59704173 and / or a single nucleotide polymorphism in linkage disequilibrium with the single nucleotide polymorphism.
(3) genotype possessing allele C of rs75548653, genotype possessing allele G of rs79694606, genotype possessing allele C of rs79489540, genotype possessing allele C of rs4235745, possessing allele C of rs78814834 Genotype, genotype with rs4705384 allele T, genotype with rs67393352 allele G, genotype with rs17110447 allele A, genotype with rs77655035 allele C, rs251468 allele C Genotype, genotype with rs80069564 allele G, genotype with rs109075 allele T, genotype with rs109076 allele T, genotype with rs251467 allele T, rs251466 allele C Genotype, genotype with rs17110463 allele C, genotype with rs251465 allele A, genotype with rs251464 allele G, genotype with rs251463 allele G, rs251462 allele A Genotype, rs4705385 Genotype with allele C, genotype with rs109077 allele T, genotype with rs112183859 allele A, genotype with rs251460 allele T, genotype with rs76390604 allele T, rs17600568 Genotype with allele C, genotype with allele T of rs10491360, genotype with allele G of rs251459, genotype with allele C of rs79435714, genotype with allele G of rs32589, genotype of rs32588 Genotype with allele T, genotype with allele T of rs32587, genotype with allele A of rs32586, genotype with allele G of rs2003602, genotype with allele A of rs32585, genotype of rs28282 Genotype with allele C, genotype with allele A of rs17653577, genotype with allele A of rs32584, genotype with allele C of rs32583, genotype with allele C of rs17110586, genotype of rs32581 Genetics with allele G Genotype with allele G of rs45560442, genotype with allele G of rs76994147, genotype with allele G of rs45520937, genotype with allele C of rs45588534, genotype with allele C of rs45543631 Genotype possessing allele G of rs75739000, genotype possessing allele G of rs6579761, genotype possessing allele T of rs1549186, genotype possessing allele C of rs1549187, genotype possessing allele A of rs1549188 , Genotype possessing allele C of rs26122, genotype possessing allele G of rs1107344, genotype possessing allele G of rs2341294, genotype possessing allele A of rs888853, genotype possessing allele C of rs7712296 , Genotype possessing allele C of rs17653703, genotype possessing allele C of rs10756813, genotype possessing allele A of rs10756814, genotype possessing allele G of rs76211545, genotype possessing allele T of rs74645810 , Rs76233 Genotype with 908 allele A, genotype with rs12376135 allele A, genotype with rs10810635 allele C, genotype with rs16935073 allele C, genotype with rs10962601 allele G, genotype possessing allele C of rs10962609, genotype possessing allele T of rs4455968, genotype possessing allele A of rs4523356, genotype possessing allele C of rs12351269, genotype possessing allele C of rs10121347, genotype possessing allele G of rs10122901, genotype possessing allele T of rs2921966, genotype possessing allele A of rs3010462, genotype possessing allele A of rs3010463, genotype possessing allele T of rs1900500, genotype possessing allele G of rs2921967, genotype possessing allele A of rs2921968, genotype possessing allele A of rs2907238, genotype possessing allele C of rs2907237, genotype possessing allele T of rs2921969, rs7902159 Genotype possessing allele T of rs7902262, genotype possessing allele A of rs3010464, genotype possessing allele A of rs1076369, genotype possessing allele T of rs1076368, genotype possessing allele T of rs1076368 Genotype with allele G, genotype with allele C of rs740595, genotype with allele G of rs733216, genotype with allele T of rs2240711, genotype with allele G of rs2240710, genotype of rs2921971 Genotype with allele T, genotype with rs12263233 allele C, genotype with rs3010467 allele C, genotype with rs12265205 allele C, genotype with rs2907231 allele C, rs3010468 Genotype with allele G, genotype with allele A of rs2921972, genotype with allele C of rs3010469, genotype with allele C of rs3010470, genotype with allele T of rs12259725, genotype of rs12259865 Own allele A Genotype, genotype with allele A of rs71500866, genotype with allele A of rs12259866, genotype with allele T of rs12259830, genotype with allele T of rs12259842, allele G of rs12245201 Genotype, genotype with rs12782444 allele T, genotype with rs3010471 allele C, genotype with rs2921973 allele T, genotype with rs3010475 allele G, rs3010476 allele A Genotype, genotype with rs3010477 allele G, genotype with rs2907230 allele T, genotype with rs3010478 allele G, genotype with rs3010479 allele C, rs3010480 allele C Genotype, genotype with rs3010481 allele C, genotype with rs2901119 allele C, genotype with rs2420327 allele C, genotype with rs3010484 allele A, rs2907229 allele T Genotype, r genotype possessing allele C of s2420328, genotype possessing allele A of rs2420329, genotype possessing allele G of rs2901120, genotype possessing allele T of rs3010488, genotype possessing allele A of rs3010489, genotype possessing allele A of rs2240709, genotype possessing allele G of s2240708, genotype possessing allele T of rs2907241, genotype possessing allele G of rs2921974, genotype possessing allele C of rs12245621, genotype possessing allele G of rs2921975, genotype possessing allele A of rs2921976, genotype possessing allele T of rs3010491, genotype possessing allele G of rs77204400, genotype possessing allele T of rs1638429, genotype possessing allele A of rs758368, genotype possessing allele T of rs4752110, genotype possessing allele C of rs7070575, genotype possessing allele C of rs12146158, genotype possessing allele T of rs10444110, rs11198112 Genotype possessing allele C, genotype possessing allele C of rs10444039, genotype possessing allele A of rs17096846, genotype possessing allele A of rs1925257, genotype possessing allele T of rs1925258, rs55927713 Genotype possessing allele T, genotype possessing allele C of rs35563099, genotype possessing allele C of rs7098111, genotype possessing allele G of rs7074192, genotype possessing allele C of rs12773211, genotype possessing allele C of rs12773211 Genotype with allele G, genotype with allele G of rs532411111, genotype with allele C of rs4994045, genotype with allele A of rs10886144, genotype with allele G of rs34878973, genotype of rs10886148 Genotype with allele G, genotype with allele C of rs4752116, genotype with allele C of rs12241016, genotype with allele A of rs11198128, genotype with allele C of rs10787798, genotype of rs10749251 Allele T Genotype possessing allele A of rs6585463, genotype possessing allele G of rs1925262, genotype possessing allele C of rs4752117, genotype possessing allele A of rs10749252, allele C of rs7085292 Genotype possessing allele C of rs4431946, genotype possessing allele C of rs4752118, genotype possessing allele A of rs4752119, genotype possessing allele G of rs10749253, allele T of rs4752120 Genotype possessing allele G of rs4751641, genotype possessing allele G of rs10787799, genotype possessing allele C of rs10886150, genotype possessing allele C of rs11198135, allele G of rs10886151 Genotype possessing allele C of rs1925264, genotype possessing allele A of rs4752122, genotype possessing allele G of rs11498896, genotype possessing allele T of rs199983705, allele T of rs11198141 Possess Genotype with allele G of rs2094020, genotype with allele C of rs10787800, genotype with allele T of rs7098136, genotype with allele G of rs12250372, allele G of rs7916406 Genotype possessing allele G of rs61866017, genotype possessing allele A of rs12103642, genotype possessing allele A of rs8066617, genotype possessing allele T of rs12942131, possessing allele C of rs10515135 Genotype possessing allele G of rs8078098, genotype possessing allele C of rs916815, genotype possessing allele T of rs8076498, genotype possessing allele C of rs59521320, possessing allele C of rs72828937 Genotype possessing allele C of rs62060342, genotype possessing allele G of rs62060343, genotype possessing allele T of rs1016984, genotype possessing allele T of rs1016985, possessing allele G of rs1016986 Inheritance Genotype with allele C of rs1016987, genotype with allele A of rs17220593, genotype with allele C of rs17821090, genotype with allele G of rs4794701, genotype with allele C of rs4794702 Genotype with allele T of rs8064252, genotype with allele T of rs17220607, genotype with allele G of rs8081915, genotype with allele G of rs4794703, heredity with allele T of rs4454703 Genotype with allele A of rs4284702, genotype with allele A of rs8067946, genotype with allele G of rs34773938, genotype with allele G of rs17220621, genotype with allele G of rs35479111 Genotype with allele C of rs62060346, genotype with allele T of rs62060347, genotype with allele G of rs62060348, genotype with allele C of rs17833789, genotype with allele G of rs9907841 Mold, rs62 Genotype possessing allele T of 060349, genotype possessing allele T of rs11079281, genotype possessing allele G of rs17821126, genotype possessing allele C of rs80243896, or inheritance possessing allele A of rs59704173 The method according to (2) above, comprising a step of determining that a subject having any one or more genotypes of a type is prone to buckwheat.
(4) A method for determining easiness of becoming a test subject's buckwheat including a step of detecting a genotype in a DNA-containing sample derived from a subject, wherein the insertion type polymorphism, the deletion type polymorphism to be detected, or Base repeat polymorphisms are rs140364236, rs77002482, rs5872148, rs143978112, rs67920508, rs11413212, rs67892375, rs5788185, rs36103789, rs35271333, rs34828951, rs10647236, rs148896299, rs11436341, rs5821164, rs112409672, rs145916, rs145916, rs145916, rs145916 The method according to (1) above, which is one or more selected insertion polymorphisms, deletion polymorphisms, or base repeat polymorphisms.
(5) genotype possessing allele ATAAGG of rs140364236, genotype possessing allele CAA of rs77002482, genotype possessing allele T of rs5872148, genotype possessing allele T of rs143978112, possessing allele C of rs67920508 Genotype, genotype with rs11413212 allele AT, genotype with rs67892375 allele A, genotype with rs5788185 allele AT, genotype with rs36103789 allele GA, rs35271333 with allele T Genotype, genotype possessing allele A of rs34828951, genotype possessing allele C of rs10647236, genotype possessing allele GTTTA of rs148896299, genotype possessing allele A of rs11436341, possessing allele CT of rs5821164 Genotype, genotype possessing allele TA of rs112409672, genotype possessing allele AC of rs111581498, gene possessing allele CCCAGCACTTTAGGAGGCTGAGG of rs145273475 , Rs530322916 genotype possessing allele C, rs200262366 allele CAA genotype, or rs548590979 genotype possessing allele AT is determined to be prone to buckwheat The method as described in said (4) including a process.
(6) The single nucleotide polymorphism according to any one of (1) to (5) and / or a single nucleotide polymorphism, an insertion polymorphism, or a deletion polymorphism that is in linkage disequilibrium with the single nucleotide polymorphism. Or a polynucleotide for determining the likelihood of becoming a test subject's buckwheat, which can be used as a probe or primer for detecting a base repeat polymorphism.
(7) A kit for determining the likelihood of becoming a test subject's buckwheat, comprising a probe and / or primer comprising the polynucleotide according to (6) above.
(8) A composition for the prevention or treatment of buckwheat that controls the expression of PPARGC1B gene, BNC2 gene, or HSPA12A gene or suppresses the action of the protein.

本発明の方法により、対象となるヒトそれぞれのソバカスになり易さを網羅的に把握することができる。また、判定用ポリヌクレオチドや判定用キットの使用により、ソバカスになり易さを簡便に把握することも可能となる。 By the method of the present invention, it is possible to comprehensively grasp the easiness of becoming a target of each target human. In addition, by using the determination polynucleotide or the determination kit, it is possible to easily grasp the easiness of becoming buckwheat.

本発明の「被験者のソバカスになり易さを判定する方法」とは、被験者由来のDNA含有試料において遺伝子多型を検出する工程を含む被験者のソバカスになり易さを判定する方法のことをいう。本発明の方法はさらに、被験者のソバカスになり易さを判定するために有用なその他の工程を含むものであっても良い。 The “method for determining the likelihood of becoming a subject's buckwheat” of the present invention refers to a method for determining the likelihood of becoming a subject's buckwheat that includes a step of detecting a genetic polymorphism in a DNA-containing sample derived from the subject. . The method of the present invention may further include other steps useful for determining the likelihood of becoming a subject's buckwheat.

ここで検出する一塩基多型とは、米国バイオテクノロジー情報センター（NCBI）SNPデータベースに登録されている表１〜７に示される群から選択される一以上の一塩基多型及び／或いは該一塩基多型と連鎖不平衡にある一塩基多型、挿入型多型、欠失型多型、又は塩基繰り返し多型のことを指す。
なお、表１〜７において“他のrs番号”とは“rs番号”で特定されるある遺伝子多型を他の番号で示したものであり、実質的に同一な遺伝子多型を示すもののことをいう。例えば遺伝子多型がrs4235745である場合、“他のrs番号”に示されるrs59586541も同じ遺伝子多型を示すものである。 The single nucleotide polymorphism detected here is one or more single nucleotide polymorphisms selected from the group shown in Tables 1 to 7 registered in the National Center for Biotechnology Information (NCBI) SNP database and / or the one single nucleotide polymorphism. It refers to a single nucleotide polymorphism, an insertion polymorphism, a deletion polymorphism, or a nucleotide repeat polymorphism that is in linkage disequilibrium with the nucleotide polymorphism.
In Tables 1 to 7, “other rs number” is a gene polymorphism identified by “rs number” indicated by another number, and indicates a substantially identical gene polymorphism. Say. For example, when the gene polymorphism is rs4235745, rs59586541 shown in “Other rs number” also indicates the same gene polymorphism.

なお、本発明における一塩基多型(Single Nucleotide Polymorphism、SNP)とは、ヒトのゲノム配列において、国際標準配列と比較して母集団中１％以上の頻度で存在する、一つの塩基が他の塩基に置換変異したものを指す。
また、本発明において連鎖不平衡にある一塩基多型とは、rs番号で特定される本発明のいずれかの一塩基多型との間の連鎖不平衡係数(r2)が0.8以上である一塩基多型をいう。 In addition, the single nucleotide polymorphism (Single Nucleotide Polymorphism, SNP) in the present invention is a human genome sequence in which one base is present at a frequency of 1% or more in the population as compared with an international standard sequence. Refers to a base substitution mutation.
In the present invention, the single nucleotide polymorphism in linkage disequilibrium is one in which the linkage disequilibrium coefficient (r2) between any single nucleotide polymorphism of the present invention specified by the rs number is 0.8 or more. A nucleotide polymorphism.

検出の対象となる一塩基多型として、例えば、表１〜６に示されるrs75548653、rs79694606、rs79489540、rs4235745（rs59586541）、rs78814834、rs4705384、rs67393352（rs67393353）、rs17110447（rs56596245,rs56659429）、rs77655035、rs251468（rs56801770）、rs80069564、rs109075（rs858453,rs1007020,rs1264258,rs2546185,rs61296391,rs74294145）、rs109076（rs707140,rs2546184）、rs251467（rs57819581）、rs251466（rs60609841）、rs17110463、rs251465（rs403267,rs13154361,rs61188717）、rs251464（rs1264257,rs13154929,rs17110504,rs52797270,rs61238636）、rs251463（rs858452,rs1264256,rs56678313,rs386568577）、rs251462（rs858451,rs57761607）、rs4705385、rs109077（rs251461,rs59527205）、rs112183859、rs251460（rs57145640,rs386568576）、rs76390604、rs17600568（rs56568254）、rs10491360（rs17110529）、rs251459、rs79435714、rs32589（rs61690281）、rs32588（rs58246058）、rs32587（rs57401245,rs386581403）、rs32586（rs60057448）、rs2003602（rs4382155）、rs32585（rs56600415,rs58534043,rs60646167）、rs28282（rs858450,rs2003603,rs17110578,rs57320177）、rs17653577、rs32584（rs56699171）、rs32583、rs17110586、rs32581（rs60318360,rs386581402）、rs45560442、rs76994147、rs45520937、rs45588534（rs61749640,rs386479590）、rs45543631（rs61749641）、rs75739000、rs6579761、rs1549186、rs1549187（rs17600714,rs59648855,rs111191920）、rs1549188、rs26122（rs61132396）、rs1107344（rs61496852）、rs2341294、rs888853（rs3733664,rs60607280）、rs7712296（rs17600756,rs57480361）、rs17653703（rs74294147）、rs10756813、rs10756814、rs76211545、rs74645810、rs76233908、rs12376135、rs10810635、rs16935073（rs58851991）、rs10962601、rs10962609、rs4455968、rs4523356、rs12351269（rs56421041,rs57566967,rs57623732）、rs10121347（rs56511114,rs57272815,rs57980018）、rs10122901、rs2921966（rs56920957,rs61448863）、rs3010462（rs9420206,rs59915014）、rs3010463、rs1900500（rs57733244）、rs2921967（rs61007768,rs539908877）、rs2921968（rs60755358）、rs2907238（rs17607611,rs59056636）、rs2907237（rs17670590,rs57955736）、rs2921969（rs3740577）、rs7902159、rs7902262、rs3010464、rs1076369（rs3010465,rs17607758）、rs1076368（rs2921970）、rs1076367（rs2240712）、rs740595（rs17676245,rs117340096）、rs733216（rs60398735,rs117624098）、rs2240711（rs60140039,rs117472092）、rs2240710（rs17676281）、rs2921971（rs9420207,rs17676299,rs57028821）、rs12263233（rs56427203,rs56726222）、rs3010467（rs17676348,rs58400337）、rs12265205、rs2907231（rs17608031,rs61545805）、rs3010468（rs59120349）、rs2921972、rs3010469、rs3010470（rs34398029,rs78020021）、rs12259725、rs12259865、rs71500866、rs12259866（rs76550855）、rs12259830、rs12259842、rs12245201、rs12782444、rs3010471（rs3010474,rs7900668,rs57493019,rs60377034）、rs2921973（rs59695131）、rs3010475（rs60606299）、rs3010476（rs17608052,rs56633076,rs58718888,rs60688190）、rs3010477（rs61404744）、rs2907230（rs17608100,rs57619168）、rs3010478（rs58031263）、rs3010479（rs17608121,rs59866691）、rs3010480（rs17676551,rs58266966）、rs3010481（rs7922265,rs60324386）、rs2901119（rs3010482,rs58219274）、rs2420327（rs3010483,rs58858827）、rs3010484（rs58519097）、rs2907229（rs60656859）、rs2420328（rs3010485,rs58393114）、rs2420329（rs3010486,rs60377255）、rs2901120（rs3010487,rs58360246）、rs3010488（rs56892899）、rs3010489（rs56739549）、rs2240709（rs58169401）、rs2240708（rs56852061）、rs2907241（rs61557392）、rs2921974（rs17608191,rs61174863）、rs12245621（rs77357165）、rs2921975（rs60132897）、rs2921976（rs60111443）、rs3010491（rs56576895,rs57709399）、rs77204400、rs1638429、rs758368、rs4752110（rs58327800）、rs7070575、rs12146158、rs10444110（rs12171898）、rs11198112（rs59053580）、rs10444039（rs11198113,rs59327236）、rs17096846（rs57440571）、rs1925257（rs57866818）、rs1925258、rs55927713（rs61865968）、rs35563099（rs58021464）、rs7098111、rs7074192（rs56690060）、rs12773211、rs555269109、rs532411111、rs4994045、rs10886144（rs12780882,rs17096889,rs61593820）、rs34878973、rs10886148、rs4752116、rs12241016（rs17641155,rs56546096,rs59220205）、rs11198128、rs10787798、rs10749251（rs59945184,rs60535959）、rs6585463（rs57109501）、rs1925262（rs17560827,rs60260766）、rs4752117、rs10749252、rs7085292、rs4431946、rs4752118、rs4752119（rs58693353）、rs10749253（rs60957769）、rs4752120（rs59116851）、rs4751641（rs17560898）、rs10787799、rs10886150、rs11198135（rs57195428）、rs10886151（rs61174077）、rs1925264（rs59929167）、rs4752122（rs7392938）、rs11498896（rs12220208,rs55748296）、rs199983705、rs11198141（rs113926753）、rs2094020（rs34172551）、rs10787800（rs57827262）、rs7098136（rs59511480）、rs12250372（rs56494925）、rs7916406（rs61125669）、rs61866017、rs12103642（rs59555040）、rs8066617（rs59289426）、rs12942131、rs10515135（rs17821066,rs58006130）、rs8078098、rs916815（rs56981026,rs74256732）、rs8076498、rs59521320（rs62060341）、rs72828937（rs73991780）、rs62060342、rs62060343、rs1016984（rs57517811）、rs1016985、rs1016986、rs1016987、rs17220593、rs17821090（rs58536422）、rs4794701（rs17821096）、rs4794702（rs386427464）、rs8064252（rs17821108）、rs17220607、rs8081915（rs58877289）、rs4794703、rs4452017、rs4284702、rs8067946、rs34773938（rs62060344）、rs17220621、rs35479111（rs62060345）、rs62060346、rs62060347、rs62060348、rs17833789、rs9907841（rs17761089,rs60842467）、rs62060349、rs11079281（rs59810598）、rs17821126（rs59904718）、rs80243896及びrs59704173（rs62060353）等が挙げられる。 As single nucleotide polymorphisms to be detected, for example, rs75548653, rs79694606, rs79489540, rs4235745 (rs59586541), rs78814834, rs4705384, rs67393352 (rs67393353), rs17110447 (rs56596245, rs56659429), rs77655035, rs251468 shown in Tables 1 to 6 (Rs56801770), rs80069564, rs109075 (rs858453, rs1007020, rs1264258, rs2546185, rs61296391, rs74294145), rs109076 (rs707140, rs2546184), rs251467 (rs57819581), rs251466 (rs60609841), rs17110463, rs251465 (rs403267, rs18813 (Rs1264257, rs13154929, rs17110504, rs52797270, rs61238636), rs251463 (rs858452, rs1264256, rs56678313, rs386568577), rs251462 (rs858451, rs57761607), rs4705385, rs109077 (rs251461, rs59527205), rs112183859, rs640, rs640 rs17600568 (rs56568254), rs10491360 (rs17110529), rs251459, rs79435714, rs32589 (rs61690281), rs32588 (rs58246058), rs32587 (rs57401245, rs386581403), rs32586 (rs60057448 ), Rs2003602 (rs4382155), rs32585 (rs56600415, rs58534043, rs60646167), rs28282 (rs858450, rs2003603, rs17110578, rs57320177), rs17653577, rs32584 (rs56699171), rs32583, rs17110586, rs32581 (rs60318360, rs386581402), rs386581402 , Rs45588534 (rs61749640, rs386479590), rs45543631 (rs61749641), rs75739000, rs6579761, rs1549186, rs1549187 (rs17600714, rs59648855, rs111191920), rs1549188, rs26122 (rs61132396), rs1107344 (rs61496852), rs854312 (Rs17600756, rs57480361), rs17653703 (rs74294147), rs10756813, rs10756814, rs76211545, rs74645810, rs76233908, rs12376135, rs10810635, rs16935073 (rs58851991), rs10962601, rs10962609, rs4455968, rs4523356, rs12351269 (34756441, 565) , rs57272815, rs57980018), rs10122901, rs2921966 (rs56920957, rs61448863), rs3010462 (rs9420206, rs59915014), rs3010463, rs1900500 (Rs57733244), rs2921967 (rs61007768, rs539908877), rs2921968 (rs60755358), rs2907238 (rs17607611, rs59056636), rs2907237 (rs17670590, rs57955736), rs2921969 (rs3740577), rs7902159, rs7902262, rs3010464 (rs1046536976, rs10465369 rs2921970), rs1076367 (rs2240712), rs740595 (rs17676245, rs117340096), rs733216 (rs60398735, rs117624098), rs2240711 (rs60140039, rs117472092), rs2240710 (rs17676281), rs2921971 (rs9420207, rs17676299, rs57026321) rs3010467 (rs17676348, rs58400337), rs12265205, rs2907231 (rs17608031, rs61545805), rs3010468 (rs59120349), rs2921972, rs3010469, rs3010470 (rs34398029), rs12259725, rs12259865, rs71500866, rs12259866 (12276530, 855 , Rs3010471 (rs3010474, rs7900668, rs57493019, rs60377034), rs2921973 (rs59695131), rs3010475 (rs60606299), rs3010476 (rs17608052, rs566 33076, rs58718888, rs60688190), rs3010477 (rs61404744), rs2907230 (rs17608100, rs57619168), rs3010478 (rs58031263), rs3010479 (rs17608121, rs59866691), rs3010480 (rs17676551, rs58266966), rs3010481 (rs7922265, rs2901 482 ), Rs2420327 (rs3010483, rs58858827), rs3010484 (rs58519097), rs2907229 (rs60656859), rs2420328 (rs3010485, rs58393114), rs2420329 (rs3010486, rs60377255), rs2901120 (rs3010487, rs58360246), rs3010488 (rs56889, 4989, 49949, rs56889) rs2240709 (rs58169401), rs2240708 (rs56852061), rs2907241 (rs61557392), rs2921974 (rs17608191, rs61174863), rs12245621 (rs77357165), rs2921975 (rs601119797), rs2921976 (rs60111443), rs3010491 (rs56576895, rs5770929, rs57204299, rs57709400 rs4752110 (rs58327800), rs7070575, rs12146158, rs10444110 (rs12171898), rs11198112 (rs59053580), rs10444039 (rs11198113, rs59327236), rs17096846 (rs57440) 571), rs1925257 (rs57866818), rs1925258, rs55927713 (rs61865968), rs35563099 (rs58021464), rs7098111, rs7074192 (rs56690060), rs12773211, rs555269109, rs532411111, rs4994045, rs10886144 (rs12780882, rs17096889, rs6173, rs17096889, rs6173,475 rs12241016 (rs17641155, rs56546096, rs59220205), rs11198128, rs10787798, rs10749251 (rs59945184, rs60535959), rs6585463 (rs57109501), rs1925262 (rs17526027, rs60260766), rs4752117, rs10749252, rs7085292, rs11841586, rs118957 ), Rs4752120 (rs59116851), rs4751641 (rs17560898), rs10787799, rs10886150, rs11198135 (rs57195428), rs10886151 (rs61174077), rs1925264 (rs59929167), rs4752122 (rs7392938), rs11498896 (rs12220208, rs8348705, 1981) rs2094020 (rs34172551), rs10787800 (rs57827262), rs7098136 (rs59511480), rs12250372 (rs56494925), rs7916406 (rs61 125669), rs61866017, rs12103642 (rs59555040), rs8066617 (rs59289426), rs12942131, rs10515135 (rs17821066, rs58006130), rs8078098, rs916815 (rs56981026, rs74256732), rs8076498, rs59521320 (rs62060341), rs72828937 (rs603034 (Rs57517811), rs1016985, rs1016986, rs1016987, rs17220593, rs17821090 (rs58536422), rs4794701 (rs17821096), rs4794702 (rs386427464), rs8064252 (rs17821108), rs17220607, rs8081915 (rs58877289), rs4794703, rs4453, 394 ), Rs17220621, rs35479111 (rs62060345), rs62060346, rs62060347, rs62060348, rs17833789, rs9907841 (rs17761089, rs60842467), rs62060349, rs11079281 (rs59810598), rs17821126 (rs59904718), rs80243896 and rs59704173 (rs62060353).

このうち一塩基多型がrs75548653の場合ではアレルがGかCであり、リスクアレルがCである。従って、被験者のソバカスになり易さは遺伝型がC/C＞G/C＞G/Gの順番となる。また、rs79694606の場合ではアレルがAかGであり、リスクアレルがGである。従って、遺伝型がG/G＞A/G＞A/Aの順番で被験者はソバカスになり易いと判定される。
なお、対応するアレルがGかCまたはAかTである一塩基多型については、リスクアレルを判定するための配列情報を表８、９に示した。本発明において“rs番号”で特定される遺伝子多型で記載しているアレルのストランドはいずれもNCBI SNPデータベースのバージョンGRCh37または米国カリフォルニア大学サンタクルーズ校（UCSC）データベースのバージョンhg19のリファレンスストランドに等しい。 If the single nucleotide polymorphism is rs75548653, the allele is G or C and the risk allele is C. Therefore, the genotype is in the order of C / C> G / C> G / G. In the case of rs79694606, the allele is A or G, and the risk allele is G. Therefore, it is determined that the subject is likely to become buckwheat in the order of genotype G / G> A / G> A / A.
For single nucleotide polymorphisms where the corresponding allele is G, C or A or T, the sequence information for determining the risk allele is shown in Tables 8 and 9. In the present invention, the strand of the allele described in the genetic polymorphism identified by the “rs number” is equal to the reference strand of NCBI SNP database version GRCh37 or the University of California Santa Cruz (UCSC) database version hg19. .

即ち、本発明の対象となる一塩基多型が次の一塩基多型である場合、１）〜２２８）のいずれか１以上の遺伝型を示す被験者であればソバカスになり易いと判定されることになる。
１）rs75548653のアレルCを保有する遺伝型、２）rs79694606のアレルGを保有する遺伝型、３）rs79489540のアレルCを保有する遺伝型、４）rs4235745のアレルCを保有する遺伝型、５）rs78814834のアレルCを保有する遺伝型、６）rs4705384のアレルTを保有する遺伝型、７）rs67393352のアレルGを保有する遺伝型、８）rs17110447のアレルAを保有する遺伝型、９）rs77655035のアレルCを保有する遺伝型、１０）rs251468のアレルCを保有する遺伝型、１１）rs80069564のアレルGを保有する遺伝型、１２）rs109075のアレルTを保有する遺伝型、１３）rs109076のアレルTを保有する遺伝型、１４）rs251467のアレルTを保有する遺伝型、１５）rs251466のアレルCを保有する遺伝型、１６）rs17110463のアレルCを保有する遺伝型、１７）rs251465のアレルAを保有する遺伝型、１８）rs251464のアレルGを保有する遺伝型、１９）rs251463のアレルGを保有する遺伝型、２０）rs251462のアレルAを保有する遺伝型、２１）rs4705385のアレルCを保有する遺伝型、２２）rs109077のアレルTを保有する遺伝型、２３）rs112183859のアレルAを保有する遺伝型、２４）rs251460のアレルTを保有する遺伝型、２５）rs76390604のアレルTを保有する遺伝型、２６）rs17600568のアレルCを保有する遺伝型、２７）rs10491360のアレルTを保有する遺伝型、２８）rs251459のアレルGを保有する遺伝型、２９）rs79435714のアレルCを保有する遺伝型、３０）rs32589のアレルGを保有する遺伝型、３１）rs32588のアレルTを保有する遺伝型、３２）rs32587のアレルTを保有する遺伝型、３３）rs32586のアレルAを保有する遺伝型、３４）rs2003602のアレルGを保有する遺伝型、３５）rs32585のアレルAを保有する遺伝型、３６）rs28282のアレルCを保有する遺伝型、３７）rs17653577のアレルAを保有する遺伝型、３８）rs32584のアレルAを保有する遺伝型、３９）rs32583のアレルCを保有する遺伝型、４０）rs17110586のアレルCを保有する遺伝型、４１）rs32581のアレルGを保有する遺伝型、４２）rs45560442のアレルGを保有する遺伝型、４３）rs76994147のアレルGを保有する遺伝型、４４）rs45520937のアレルGを保有する遺伝型、４５）rs45588534のアレルCを保有する遺伝型、４６）rs45543631のアレルCを保有する遺伝型、４７）rs75739000のアレルGを保有する遺伝型、４８）rs6579761のアレルGを保有する遺伝型、４９）rs1549186のアレルTを保有する遺伝型、５０）rs1549187のアレルCを保有する遺伝型、５１）rs1549188のアレルAを保有する遺伝型、５２）rs26122のアレルCを保有する遺伝型、５３）rs1107344のアレルGを保有する遺伝型、５４）rs2341294のアレルGを保有する遺伝型、５５）rs888853のアレルAを保有する遺伝型、５６）rs7712296のアレルCを保有する遺伝型、５７）rs17653703のアレルCを保有する遺伝型、５８）rs10756813のアレルCを保有する遺伝型、５９）rs10756814のアレルAを保有する遺伝型、６０）rs76211545のアレルGを保有する遺伝型、６１）rs74645810のアレルTを保有する遺伝型、６２）rs76233908のアレルAを保有する遺伝型、６３）rs12376135のアレルAを保有する遺伝型、６４）rs10810635のアレルCを保有する遺伝型、６５）rs16935073のアレルCを保有する遺伝型、６６）rs10962601のアレルGを保有する遺伝型、６７）rs10962609のアレルCを保有する遺伝型、６８）rs4455968のアレルTを保有する遺伝型、６９）rs4523356のアレルAを保有する遺伝型、７０）rs12351269のアレルCを保有する遺伝型、７１）rs10121347のアレルCを保有する遺伝型、７２）rs10122901のアレルGを保有する遺伝型、７３）rs2921966のアレルTを保有する遺伝型、７４）rs3010462のアレルAを保有する遺伝型、７５）rs3010463のアレルAを保有する遺伝型、７６）rs1900500のアレルTを保有する遺伝型、７７）rs2921967のアレルGを保有する遺伝型、７８）rs2921968のアレルAを保有する遺伝型、７９）rs2907238のアレルAを保有する遺伝型、８０）rs2907237のアレルCを保有する遺伝型、８１）rs2921969のアレルTを保有する遺伝型、８２）rs7902159のアレルGを保有する遺伝型、８３）rs7902262のアレルTを保有する遺伝型、８４）rs3010464のアレルAを保有する遺伝型、８５）rs1076369のアレルAを保有する遺伝型、８６）rs1076368のアレルTを保有する遺伝型、８７）rs1076367のアレルGを保有する遺伝型、８８）rs740595のアレルCを保有する遺伝型、８９）rs733216のアレルGを保有する遺伝型、９０）rs2240711のアレルTを保有する遺伝型、９１）rs2240710のアレルGを保有する遺伝型、９２）rs2921971のアレルTを保有する遺伝型、９３）rs12263233のアレルCを保有する遺伝型、９４）rs3010467のアレルCを保有する遺伝型、９５）rs12265205のアレルCを保有する遺伝型、９６）rs2907231のアレルCを保有する遺伝型、９７）rs3010468のアレルGを保有する遺伝型、９８）rs2921972のアレルAを保有する遺伝型、９９）rs3010469のアレルCを保有する遺伝型、１００）rs3010470のアレルCを保有する遺伝型、１０１）rs12259725のアレルTを保有する遺伝型、１０２）rs12259865のアレルAを保有する遺伝型、１０３）rs71500866のアレルAを保有する遺伝型、１０４）rs12259866のアレルAを保有する遺伝型、１０５）rs12259830のアレルTを保有する遺伝型、１０６）rs12259842のアレルTを保有する遺伝型、１０７）rs12245201のアレルGを保有する遺伝型、１０８）rs12782444のアレルTを保有する遺伝型、１０９）rs3010471のアレルCを保有する遺伝型、１１０）rs2921973のアレルTを保有する遺伝型、１１１）rs3010475のアレルGを保有する遺伝型、１１２）rs3010476のアレルAを保有する遺伝型、１１３）rs3010477のアレルGを保有する遺伝型、１１４）rs2907230のアレルTを保有する遺伝型、１１５）rs3010478のアレルGを保有する遺伝型、１１６）rs3010479のアレルCを保有する遺伝型、１１７）rs3010480のアレルCを保有する遺伝型、１１８）rs3010481のアレルCを保有する遺伝型、１１９）rs2901119のアレルCを保有する遺伝型、１２０）rs2420327のアレルCを保有する遺伝型、１２１）rs3010484のアレルAを保有する遺伝型、１２２）rs2907229のアレルTを保有する遺伝型、１２３）rs2420328のアレルCを保有する遺伝型、１２４）rs2420329のアレルAを保有する遺伝型、１２５）rs2901120のアレルGを保有する遺伝型、１２６）rs3010488のアレルTを保有する遺伝型、１２７）rs3010489のアレルAを保有する遺伝型、１２８）rs2240709のアレルAを保有する遺伝型、１２９）rs2240708のアレルGを保有する遺伝型、１３０）rs2907241のアレルTを保有する遺伝型、１３１）rs2921974のアレルGを保有する遺伝型、１３２）rs12245621のアレルCを保有する遺伝型、１３３）rs2921975のアレルGを保有する遺伝型、１３４）rs2921976のアレルAを保有する遺伝型、１３５）rs3010491のアレルTを保有する遺伝型、１３６）rs77204400のアレルGを保有する遺伝型、１３７）rs1638429のアレルTを保有する遺伝型、１３８）rs758368のアレルAを保有する遺伝型、１３９）rs4752110のアレルTを保有する遺伝型、１４０）rs7070575のアレルCを保有する遺伝型、１４１）rs12146158のアレルCを保有する遺伝型、１４２）rs10444110のアレルTを保有する遺伝型、１４３）rs11198112のアレルCを保有する遺伝型、１４４）rs10444039のアレルCを保有する遺伝型、１４５）rs17096846のアレルAを保有する遺伝型、１４６）rs1925257のアレルAを保有する遺伝型、１４７）rs1925258のアレルTを保有する遺伝型、１４８）rs55927713のアレルTを保有する遺伝型、１４９）rs35563099のアレルCを保有する遺伝型、１５０）rs7098111のアレルCを保有する遺伝型、１５１）rs7074192のアレルGを保有する遺伝型、１５２）rs12773211のアレルCを保有する遺伝型、１５３）rs555269109のアレルGを保有する遺伝型、１５４）rs532411111のアレルGを保有する遺伝型、１５５）rs4994045のアレルCを保有する遺伝型、１５６）rs10886144のアレルAを保有する遺伝型、１５７）rs34878973のアレルGを保有する遺伝型、１５８）rs10886148のアレルGを保有する遺伝型、１５９）rs4752116のアレルCを保有する遺伝型、１６０）rs12241016のアレルCを保有する遺伝型、１６１）rs11198128のアレルAを保有する遺伝型、１６２）rs10787798のアレルCを保有する遺伝型、１６３）rs10749251のアレルTを保有する遺伝型、１６４）rs6585463のアレルAを保有する遺伝型、１６５）rs1925262のアレルGを保有する遺伝型、１６６）rs4752117のアレルCを保有する遺伝型、１６７）rs10749252のアレルAを保有する遺伝型、１６８）rs7085292のアレルCを保有する遺伝型、１６９）rs4431946のアレルCを保有する遺伝型、１７０）rs4752118のアレルCを保有する遺伝型、１７１）rs4752119のアレルAを保有する遺伝型、１７２）rs10749253のアレルGを保有する遺伝型、１７３）rs4752120のアレルTを保有する遺伝型、１７４）rs4751641のアレルGを保有する遺伝型、１７５）rs10787799のアレルGを保有する遺伝型、１７６）rs10886150のアレルCを保有する遺伝型、１７７）rs11198135のアレルCを保有する遺伝型、１７８）rs10886151のアレルGを保有する遺伝型、１７９）rs1925264のアレルCを保有する遺伝型、１８０）rs4752122のアレルAを保有する遺伝型、１８１）rs11498896のアレルGを保有する遺伝型、１８２）rs199983705のアレルTを保有する遺伝型、１８３）rs11198141のアレルTを保有する遺伝型、１８４）rs2094020のアレルGを保有する遺伝型、１８５）rs10787800のアレルCを保有する遺伝型、１８６）rs7098136のアレルTを保有する遺伝型、１８７）rs12250372のアレルGを保有する遺伝型、１８８）rs7916406のアレルGを保有する遺伝型、１８９）rs61866017のアレルGを保有する遺伝型、１９０）rs12103642のアレルAを保有する遺伝型、１９１）rs8066617のアレルAを保有する遺伝型、１９２）rs12942131のアレルTを保有する遺伝型、１９３）rs10515135のアレルCを保有する遺伝型、１９４）rs8078098のアレルGを保有する遺伝型、１９５）rs916815のアレルCを保有する遺伝型、１９６）rs8076498のアレルTを保有する遺伝型、１９７）rs59521320のアレルCを保有する遺伝型、１９８）rs72828937のアレルCを保有する遺伝型、１９９）rs62060342のアレルCを保有する遺伝型、２００）rs62060343のアレルGを保有する遺伝型、２０１）rs1016984のアレルTを保有する遺伝型、２０２）rs1016985のアレルTを保有する遺伝型、２０３）rs1016986のアレルGを保有する遺伝型、２０４）rs1016987のアレルCを保有する遺伝型、２０５）rs17220593のアレルAを保有する遺伝型、２０６）rs17821090のアレルCを保有する遺伝型、２０７）rs4794701のアレルGを保有する遺伝型、２０８）rs4794702のアレルCを保有する遺伝型、２０９）rs8064252のアレルTを保有する遺伝型、２１０）rs17220607のアレルTを保有する遺伝型、２１１）rs8081915のアレルGを保有する遺伝型、２１２）rs4794703のアレルGを保有する遺伝型、２１３）rs4452017のアレルTを保有する遺伝型、２１４）rs4284702のアレルAを保有する遺伝型、２１５）rs8067946のアレルAを保有する遺伝型、２１６）rs34773938のアレルGを保有する遺伝型、２１７）rs17220621のアレルGを保有する遺伝型、２１８）rs35479111のアレルGを保有する遺伝型、２１９）rs62060346のアレルCを保有する遺伝型、２２０）rs62060347のアレルTを保有する遺伝型、２２１）rs62060348のアレルGを保有する遺伝型、２２２）rs17833789のアレルCを保有する遺伝型、２２３）rs9907841のアレルGを保有する遺伝型、２２４）rs62060349のアレルTを保有する遺伝型、２２５）rs11079281のアレルTを保有する遺伝型、２２６）rs17821126のアレルGを保有する遺伝型、２２７）rs80243896のアレルCを保有する遺伝型、２２８）rs59704173のアレルAを保有する遺伝型。 That is, when the single nucleotide polymorphism to be the subject of the present invention is the following single nucleotide polymorphism, it is determined that a subject exhibiting any one or more genotypes of 1) to 228) is likely to be buckwheat. It will be.
1) genotype possessing allele C of rs75548653, 2) genotype possessing allele G of rs79694606, 3) genotype possessing allele C of rs79489540, 4) genotype possessing allele C of rs4235745, 5) genotype possessing allele C of rs78814834, 6) genotype possessing allele T of rs4705384, 7) genotype possessing allele G of rs67393352, 8) genotype possessing allele A of rs17110447, 9) genotype possessing allele A of rs17110447 Genotype with allele C, 10) genotype with allele C of rs251468, 11) genotype with allele G of rs80069564, 12) genotype with allele T of rs109075, 13) allele T of rs109076 14) genotype with rs251467 allele T, 15) genotype with rs251466 allele C, 16) genotype with rs17110463 allele C, 17) rs251465 allele A 18) Keep allele G of rs251464 19) genotype possessing allele G of rs251463, 20) genotype possessing allele A of rs251462, 21) genotype possessing allele C of rs4705385, 22) inheritance possessing allele T of rs109077 23) genotype possessing allele A of rs112183859, 24) genotype possessing allele T of rs251460, 25) genotype possessing allele T of rs76390604, 26) genotype possessing allele C of rs17600568, 27) genotype possessing allele T of rs10491360, 28) genotype possessing allele G of rs251459, 29) genotype possessing allele C of rs79435714, 30) genotype possessing allele G of rs32589, 31) genotype possessing allele T of rs32588, 32) genotype possessing allele T of rs32587, 33) genotype possessing allele A of rs32586, 34) genotype possessing allele G of rs2003602, 35) genotype possessing allele G of rs2003602 Genotype with allele A, 3 ) Genotype possessing allele C of rs28282, 37) genotype possessing allele A of rs17653577, 38) genotype possessing allele A of rs32584, 39) genotype possessing allele C of rs32583, 40) rs17110586 Genotype with allele C of 41, genotype with allele G of rs32581, 42) genotype with allele G of rs45560442, 43) genotype with allele G of rs76994147, 44) allele of rs45520937 Genotype with G, 45) genotype with rs45588534 allele C, 46) genotype with rs45543631 allele C, 47) genotype with rs75739000 allele G, 48) allele G with rs6579761 Genotype possessed, 49) genotype possessing allele T of rs1549186, 50) genotype possessing allele C of rs1549187, 51) genotype possessing allele A of rs1549188, 52) possessing allele C of rs26122 Genotype, 53) rs1107344 Genotype possessing allele G, 54) genotype possessing allele G of rs2341294, 55) genotype possessing allele A of rs888853, 56) genotype possessing allele C of rs7712296, 57) allele C of rs17653703 58) genotype possessing allele C of rs10756813, 59) genotype possessing allele A of rs10756814, 60) genotype possessing allele G of rs76211545, 61) possessing allele T of rs74645810 62) genotype possessing allele A of rs76233908, 63) genotype possessing allele A of rs12376135, 64) genotype possessing allele C of rs10810635, 65) inheritance possessing allele C of rs16935073 66) genotype possessing allele G of rs10962601, 67) genotype possessing allele C of rs10962609, 68) genotype possessing allele T of rs4455968, 69) genotype possessing allele A of rs4523356, 70) rs12351269 Genotype possessing allele C, 71) genotype possessing allele C of rs10121347, 72) genotype possessing allele G of rs10122901, 73) genotype possessing allele T of rs2921966, 74) allele A of rs3010462 75) genotype possessing allele A of rs3010463, 76) genotype possessing allele T of rs1900500, 77) genotype possessing allele G of rs2921967, 78) possessing allele A of rs2921968 79) genotype possessing allele A of rs2907238, 80) genotype possessing allele C of rs2907237, 81) genotype possessing allele T of rs2921969, 82) inheritance possessing allele G of rs7902159 83) genotype possessing allele T of rs7902262, 84) genotype possessing allele A of rs3010464, 85) genotype possessing allele A of rs1076369, 86) genotype possessing allele T of rs1076368, 87) Allele G of rs1076367 88) genotype possessing allele C of rs740595, 89) genotype possessing allele G of rs733216, 90) genotype possessing allele T of rs2240711, 91) inheritance possessing allele G of rs2240710 92) genotype possessing allele C of rs2921971, 93) genotype possessing allele C of rs12263233, 94) genotype possessing allele C of rs3010467, 95) genotype possessing allele C of rs12265205, 96) genotype possessing allele C of rs2907231, 97) genotype possessing allele G of rs3010468, 98) genotype possessing allele A of rs2921972, 99) genotype possessing allele C of rs3010469, 100) genotype possessing allele C of rs3010470, 101) genotype possessing allele T of rs12259725, 102) genotype possessing allele A of rs12259865, 103) genotype possessing allele A of rs71500866, 104) genotype possessing allele A of rs71500866 Allele Genotype possessing A, 105) genotype possessing allele T of rs12259830, 106) genotype possessing allele T of rs12259842, 107) genotype possessing allele G of rs12245201, 108) allele T of rs12782444 109) genotype possessing allele C of rs3010471, 110) genotype possessing allele T of rs2921973, 111) genotype possessing allele G of rs3010475, 112) possessing allele A of rs3010476 Genotype, 113) genotype possessing allele G of rs3010477, 114) genotype possessing allele T of rs2907230, 115) genotype possessing allele G of rs3010478, 116) genotype possessing allele C of rs3010479 117) genotype possessing allele C of rs3010480, 118) genotype possessing allele C of rs3010481, 119) genotype possessing allele C of rs2901119, 120) remnant possessing allele C of rs2420327 121) genotype possessing allele A of rs3010484, 122) genotype possessing allele T of rs2907229, 123) genotype possessing allele C of rs2420328, 124) genotype possessing allele A of rs2420329, 125) genotype possessing allele G of rs2901120, 126) genotype possessing allele T of rs3010488, 127) genotype possessing allele A of rs3010489, 128) genotype possessing allele A of rs2240709, 129) genotype possessing allele G of rs2240708, 130) genotype possessing allele T of rs2907241, 131) genotype possessing allele G of rs2921974, 132) genotype possessing allele C of rs12245621, 133) of genotype possessing allele C Genotype possessing allele G, 134) genotype possessing allele A of rs2921976, 135) genotype possessing allele T of rs3010491, 136) genotype possessing allele G of rs77204400, 137) rs Genotype with allele T of 1638429, 138) genotype with allele A of rs758368, 139) genotype with allele T of rs4752110, 140) genotype with allele C of rs7070575, 141) rs12146158 of genotype Genotype with allele C, 142) genotype with allele T of rs10444110, 143) genotype with allele C of rs11198112, 144) genotype with allele C of rs10444039, 145) allele A of rs17096846 146) genotype possessing allele T of rs1925257, 147) genotype possessing allele T of rs1925258, 148) genotype possessing allele T of rs55927713, 149) possessing allele C of rs35563099 150) genotype possessing allele C of rs7098111, 151) genotype possessing allele G of rs7074192, 152) genotype possessing allele C of rs12773211, 153) allele of rs555269109 Genotype possessing allele G of 154) genotype possessing allele G of rs532411111, 155) genotype possessing allele C of rs4994045, 156) genotype possessing allele A of rs10886144, 157) allele G of rs34878973 158) genotype possessing allele G of rs10886148, 159) genotype possessing allele C of rs4752116, 160) genotype possessing allele C of rs12241016, 161) possessing allele A of rs11198128 162) genotype with allele C of rs10787798, 163) genotype with allele T of rs10749251, 164) genotype with allele A of rs6585463, 165) heredity with allele G of rs1925262 166) genotype with rs4752117 allele C, 167) genotype with rs10749252 allele A, 168) genotype with rs7085292 allele C, 169) rs4431946 with allele C 170) genotype possessing allele C of rs4752118, 171) genotype possessing allele A of rs4752119, 172) genotype possessing allele G of rs10749253, 173) inheritance possessing allele T of rs4752120 174) genotype possessing allele G of rs4751641 175) genotype possessing allele G of rs10787799, 176) genotype possessing allele C of rs10886150, 177) genotype possessing allele C of rs11198135, 178) genotype possessing allele G of rs10886151, 179) genotype possessing allele C of rs1925264, 180) genotype possessing allele A of rs4752122, 181) genotype possessing allele G of rs11498896, 182) genotype possessing allele T of rs199983705, 183) genotype possessing allele T of rs11198141, 184) genotype possessing allele G of rs2094020, 185) inheritance possessing allele C of rs10787800 186) genotype possessing allele T of rs7098136, 187) genotype possessing allele G of rs12250372, 188) genotype possessing allele G of rs7916406, 189) genotype possessing allele G of rs61866017, 190 ) Genotype possessing allele A of rs12103642, 191) genotype possessing allele A of rs8066617, 192) genotype possessing allele T of rs12942131, 193) genotype possessing allele C of rs10515135, 194) rs8078098 Genotype with allele G of 195) genotype with allele C of rs916815, 196) genotype with allele T of rs8076498, 197) genotype with allele C of rs59521320, 198) allele of rs72828937 Genotype possessing C, 199) genotype possessing allele C of rs62060342, 200) genotype possessing allele G of rs62060343, 201) genotype possessing allele T of rs1016984, 202) genotype possessing allele T of rs1016985, 203) genotype possessing allele G of rs1016986, 204) genotype possessing allele C of rs1016987, 205) genotype possessing allele A of rs17220593, 206) genotype possessing allele A of rs17220593 Genotype with allele C, 207) genotype with allele G of rs4794701, 208) genotype with allele C of rs4794702, 209) genotype with allele T of rs8064252, 210) allele T of rs17220607 211) genotype with allele G of rs8081915, 212) genotype with allele G of rs4794703, 213) genotype with allele T of rs4452017, 214) allele A of rs4284702 215) genotype possessing allele A of rs8067946, 216) genotype possessing allele G of rs34773938, 217) genotype possessing allele G of rs17220621, 218) allele of rs35479111 219) genotype possessing allele C of rs62060346, 220) genotype possessing allele T of rs62060347, 221) genotype possessing allele G of rs62060348, 222) allele C of rs17833789 223) genotype with rs9907841 allele G, 224) genotype with rs62060349 allele T, 225) genotype with rs11079281 allele T, 226) rs17821126 with allele G 227) genotype possessing allele C of rs80243896, 228) genotype possessing allele A of rs59704173.

また、本発明の検出の対象には挿入型多型、欠失型多型、又は塩基繰り返し多型も含まれる。このような多型は例えば、表７に示されるrs140364236（rs141163096）、rs77002482（rs146771303）、rs5872148（rs35367267,rs147516092）、rs143978112（rs202020135）、rs67920508（rs67920509）、rs11413212（rs34108610,rs201393757）、rs67892375、rs5788185（rs138967723）、rs36103789（rs57886431、rs67118840、rs67151917、rs75420048、rs139555153、rs137872299、rs67118841、rs67118842、rs67151918、rs67151919、rs67151920、rs67151921、rs147385582）、rs35271333（rs67254336,rs369938869）、rs34828951（rs59182089,rs68159202,rs112784299,rs367546267）、rs10647236、rs148896299、rs11436341（rs66964517,rs149882111）、rs5821164（rs35399532,rs143537238,rs370639048）、rs112409672（rs140948233,rs373942425）、rs111581498（rs113291854,rs146436420,rs377682640）、rs145273475、rs530322916、rs200262366及びrs548590979等が挙げられる。 Moreover, insertion polymorphisms, deletion polymorphisms, or base repeat polymorphisms are also included in the targets of detection of the present invention. Such polymorphisms are, for example, rs140364236 (rs141163096), rs77002482 (rs146771303), rs5872148 (rs35367267, rs147516092), rs143978112 (rs202020135), rs67920508 (rs67920509), rs11413212 (rs34108610, rs201393757), rs678185, rs5 shown in Table 7 (Rs138967723), rs36103789 (rs57886431, rs67118840, rs67151917, rs75420048, rs139555153, rs137872299, rs67118841, rs67118842, rs67151918, rs67151919, rs67151920, rs67151921, rs147385582), rs35271333 (rs67254336, rs3699388951, rs369938869 Rs10647236, rs148896299, rs11436341 (rs66964517, rs149882111), rs5821164 (rs35399532, rs143537238, rs370639048), rs112409672 (rs140948233, rs373942425), rs111581498 (rs113291854, rs146436420, rs377682640), rs145273475, rs 362

このうち挿入型多型、欠失型多型、又は塩基繰り返し多型がrs140364236の場合では、アレルがAかATAAGGであり、リスクアレルがATAAGGである。従って、被験者のソバカスになり易さは遺伝型がATAAGG/ATAAGG＞A/ATAAGG＞A/Aの順番で高いと判定される。また、rs77002482の場合ではアレルがCかCAAであり、リスクアレルがCAAである。従って、遺伝型がCAA/CAA＞C/CAA＞C/Cの順番で被験者のソバカスになり易さが高いと判定することになる。 Of these, when the insertion polymorphism, deletion polymorphism, or base repeat polymorphism is rs140364236, the allele is A or ATAAGG, and the risk allele is ATAAGG. Therefore, it is determined that the genotype is more likely in the order of TAAAGG / ATAAGG> A / ATAAGG> A / A. In the case of rs77002482, the allele is C or CAA, and the risk allele is CAA. Therefore, it is determined that the genotype is likely to become a test subject's buckwheat in the order of CAA / CAA> C / CAA> C / C.

即ち、本発明の検出対象が次の挿入型多型、欠失型多型、又は塩基繰り返し多型である場合、１）〜２１）のいずれか１以上の遺伝型を示す被験者であればソバカスになりやすいと判定されることになる。
１）rs140364236のアレルATAAGGを保有する遺伝子型、２）rs77002482のアレルCAAを保有する遺伝子型、３）rs5872148のアレルTを保有する遺伝子型、４）rs143978112のアレルTを保有する遺伝子型、５）rs67920508のアレルCを保有する遺伝子型、６）rs11413212のアレルATを保有する遺伝子型、７）rs67892375のアレルAを保有する遺伝子型、８）rs5788185のアレルATを保有する遺伝子型、９）rs36103789のアレルGAを保有する遺伝子型、１０）rs35271333のアレルTを保有する遺伝子型、１１）rs34828951のアレルAを保有する遺伝子型、１２）rs10647236のアレルCを保有する遺伝子型、１３）rs148896299のアレルGTTTAを保有する遺伝子型、１４）rs11436341のアレルAを保有する遺伝子型、１５）rs5821164のアレルCTを保有する遺伝子型、１６）rs112409672のアレルTAを保有する遺伝子型、１７）rs111581498のアレルACを保有する遺伝子型、１８）rs145273475のアレルCCCAGCACTTTAGGAGGCTGAGGを保有する遺伝子型、１９）rs530322916のアレルCを保有する遺伝子型、２０）rs200262366のアレルCAAを保有する遺伝子型、２１）rs548590979のアレルATを保有する遺伝子型。 That is, if the detection target of the present invention is the following insertion polymorphism, deletion polymorphism, or base repeat polymorphism, if the subject exhibits any one or more genotypes of 1) to 21) It will be judged that it is easy to become.
1) Genotype possessing allele ATAAGG of rs140364236, 2) Genotype possessing allele CAA of rs77002482, 3) Genotype possessing allele T of rs5872148, 4) Genotype possessing allele T of rs143978112, 5) genotype possessing allele C of rs67920508, 6) genotype possessing allele AT of rs11413212, 7) genotype possessing allele A of rs67892375, 8) genotype possessing allele AT of rs5788185, 9) genotype possessing allele AT of rs5788185, 9) Genotype possessing allele GA, 10) genotype possessing allele T of rs35271333, 11) genotype possessing allele A of rs34828951, 12) genotype possessing allele C of rs10647236, 13) allele GTTTA of rs148896299 14) genotype possessing allele A of rs11436341, 15) genotype possessing allele CT of rs5821164, 16) genotype possessing allele TA of rs112409672, 17) rs1115814 Genotype possessing 98 alleles AC, 18) genotype possessing alleles CCCAGCACTTTAGGAGGCTGAGG of rs145273475, 19) genotype possessing allele C of rs530322916, 20) genotype possessing allele CAA of rs200262366, 21) rs548590979 Genotype that possesses allele AT.

本発明の方法の判定対象となる被験者はヒトであれば良く、アジア人種、特に東アジア人、さらには日本人であることが好ましく、性別は問わない。
また「被験者由来のDNA試料」とは、ゲノムDNA、cDNA、又はmRNAのいずれであっても良く、ソバカスになり易さを判定する対象の被験者から得られるものであれば良く、例えば、唾液、唾、髪の毛、血液、リンパ液、骨髄液、精液、腹腔液、尿等の体液、髪の毛等を由来として調製される試料等が挙げられる。 The subject to be determined by the method of the present invention may be a human, preferably an Asian race, particularly an East Asian, and even a Japanese, regardless of gender.
Further, the “subject-derived DNA sample” may be any of genomic DNA, cDNA, or mRNA, as long as it is obtained from the subject subject to determine the likelihood of becoming a buckwheat, such as saliva, Examples include samples prepared from saliva, hair, blood, lymph, bone marrow, semen, peritoneal fluid, urine and other body fluids, hair and the like.

本発明の一塩基多型及び／或いは該一塩基多型と連鎖不平衡にある一塩基多型、挿入型多型、欠失型多型、又は塩基繰り返し多型の検出にあたり、従来知られているいずれの方法を用いても良く、例えばTaqMan（登録商標）PCR、LAMP法等のPCRによってこれらの遺伝子多型を含む断片を増幅する方法やDNAシーケンサー等で塩基配列を直接決定し、これらの遺伝子多型を検出する方法等が挙げられる。また、DNAチップやGeneチップ等のマイクロアレイによる検出方法を使用しても良い。 Conventionally known for detection of single nucleotide polymorphisms and / or single nucleotide polymorphisms, insertion polymorphisms, deletion polymorphisms, or base repeat polymorphisms in linkage disequilibrium with the single nucleotide polymorphisms of the present invention. Any of these methods may be used, for example, a method of amplifying a fragment containing these gene polymorphisms by PCR such as TaqMan (registered trademark) PCR or LAMP method, or by directly determining the nucleotide sequence with a DNA sequencer, etc. Examples include a method for detecting a gene polymorphism. Alternatively, a detection method using a microarray such as a DNA chip or a Gene chip may be used.

本発明の「被験者のソバカスになり易さの判定用ポリヌクレオチド」とは、本発明の検出対象として特定されている一塩基多型及び／或いは該一塩基多型と連鎖不平衡にある一塩基多型、挿入型多型、欠失型多型、又は塩基繰り返し多型の塩基配列を含み得るポリヌクレオチドを指す。
例えば検出対象となる遺伝子多型であるrs75548653の場合は、G/G、C/G、C/Cのいずれに該当するか検出するために、その箇所の塩基配列を含むポリヌクレオチドとなる。このポリヌクレオチドは検出対象となる一塩基多型及びこれに連続する少なくとも15〜30塩基対からなる塩基配列であることが好ましく、これに相補的な塩基配列も本発明の「被験者のソバカスになり易さの判定用ポリヌクレオチド」に該当し得る。
そして、この「被験者のソバカスになり易さの判定用ポリヌクレオチド」は、一塩基多型及び／又は該一塩基多型と連鎖不平衡にある一塩基多型を検出するためのプローブ又はプライマーとして用いることができる。 The “polynucleotide for determining the likelihood of becoming a subject's buckwheat” of the present invention refers to a single nucleotide polymorphism specified as a detection target of the present invention and / or a single nucleotide in linkage disequilibrium with the single nucleotide polymorphism. It refers to a polynucleotide that may contain a base sequence of polymorphism, insertion polymorphism, deletion polymorphism, or base repeat polymorphism.
For example, in the case of rs75548653, which is a gene polymorphism to be detected, in order to detect whether it corresponds to G / G, C / G, or C / C, it becomes a polynucleotide containing the nucleotide sequence at that location. The polynucleotide is preferably a single nucleotide polymorphism to be detected and a base sequence consisting of at least 15 to 30 base pairs continuous thereto, and a base sequence complementary thereto is also the “subject of the subject” of the present invention. It may correspond to “easiness determination polynucleotide”.
This “polynucleotide for determining the likelihood of becoming a test subject's buckwheat” is a probe or primer for detecting a single nucleotide polymorphism and / or a single nucleotide polymorphism in linkage disequilibrium with the single nucleotide polymorphism. Can be used.

本発明の「被験者のソバカスになり易さの判定用キット」とは、「被験者のソバカスになり易さの判定用ポリヌクレオチド」からなるプローブ及び／又はプライマーを少なくとも含むキットのことをいう。このキットはさらに、一塩基多型及び／又は該一塩基多型と連鎖不平衡にある一塩基多型、挿入型多型、欠失型多型、又は塩基繰り返し多型を検出する各方法に適した試薬等を含むものであってもよく、支持体に固定化されたマイクロアレイ等としてキットに含まれてもよい。 The “kit for determining easiness of becoming a test subject's buckwheat” of the present invention refers to a kit including at least a probe and / or a primer comprising “a polynucleotide for determining the easiness of becoming a test subject's fungus”. This kit is further used for each method of detecting a single nucleotide polymorphism and / or a single nucleotide polymorphism, an insertion polymorphism, a deletion polymorphism, or a nucleotide repeat polymorphism in linkage disequilibrium with the single nucleotide polymorphism. It may contain a suitable reagent or the like, and may be included in the kit as a microarray or the like immobilized on a support.

本発明の「ソバカスの予防又は治療のための組成物」とは、ソバカスの発生の予防や既に発生しているソバカスを治療するための組成物のことをいう。この組成物は、PPARGC1B遺伝子、BNC2遺伝子、又はHSPA12A遺伝子の発現を制御することでこれらのタンパク質の合成を抑制したり、合成されたタンパク質の作用を抑制したりすることができる。
特にPPARgammma又はエストロゲン受容体を刺激するタンパク質をコードする遺伝子であるPPARGC1B遺伝子の発現を制御できる組成物であることが好ましい。
このような組成物は、ソバカスの予防や治療のための化粧品、医薬品等の有効成分とすることができ、この化粧品、医薬品等は全身又は局所的に投与することが可能である。 The “composition for the prevention or treatment of buckwheat” of the present invention refers to a composition for preventing the occurrence of buckwheat or treating buckwheat that has already occurred. This composition can suppress the synthesis of these proteins or the action of the synthesized proteins by controlling the expression of the PPARGC1B gene, the BNC2 gene, or the HSPA12A gene.
In particular, a composition capable of controlling the expression of the PPARGC1B gene, which is a gene encoding a protein that stimulates PPARgammma or the estrogen receptor, is preferable.
Such a composition can be used as an active ingredient such as cosmetics and pharmaceuticals for the prevention and treatment of buckwheat, and the cosmetics and pharmaceuticals can be administered systemically or locally.

以下、実施例をあげて本発明をさらに詳細に説明するが、本発明はこれらに限定されるものではない。 EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated further in detail, this invention is not limited to these.

１．DNAサンプル
株式会社エムティーアイの女性のヘルスケアに関するウェブサイト及びアプリの使用者であり、かつ、任意に募集したソバカス（形質）に関するアンケートに回答した者をDNAサンプル提供の対象者とした。この対象者は2回の募集によって集められ、1回目のステージ(以下、LL01と示す場合がある)では12085名、2回目のステージ(以下、LL02と示す場合がある)では14407名が集まった。
このうち、eメールアドレス、個人情報等によるスクリーニングを経て、LL01では7000名、LL02では9321名がサンプル提供の対象者となった。
なお、ソバカスに関するアンケートはSurvey Monkey（http://www.surveymonkey.com）によって作成され、オンラインにより対象者から回答を受けた。 1. DNA samples Persons who were users of websites and apps related to women's health care at MTI Co., Ltd., and who responded to questionnaires regarding sobacas (characters) that were voluntarily recruited were targeted for DNA sample provision. This subject was collected by two recruits, 12085 people gathered in the first stage (hereinafter sometimes referred to as LL01), and 14407 people gathered in the second stage (hereinafter sometimes designated LL02). .
Of these, after screening based on e-mail addresses, personal information, etc., 7000 LL01 and 9321 LL02 were sampled.
The survey on Sobacus was created by Survey Monkey (http://www.surveymonkey.com) and received online responses from the subject.

LL01の対象者のDNAサンプルは、唾液採取キット（OraGene(登録商標） DNA；DNA Genotek社）により2015年3月から6月まで郵送にて集められた（n_LL01=5882）。また、LL02の対象者のサンプルは同様に2015年9月から2016年4月の間に集められた（n_LL02=5783）。
本発明にあたり、同意書、アンケート項目、及び遺伝型判定について、つくば国際臨床薬理クリニックの倫理審査委員会によって承認を受けた。同意書のサインにて同意を受けたサンプル提供者よりサンプル収集を行い、遺伝型判定、ソバカスについてのアンケート、及びゲノムワイド関連解析による形質分析を行った。 DNA samples of subjects of LL01 were collected by mail from March to June 2015 (n _LL01 = 5882) using a saliva collection kit (OraGene (registered trademark) DNA; DNA Genotek). A sample of LL02 subjects was also collected between September 2015 and April 2016 (n _LL02 = 5783).
In the present invention, consent forms, questionnaire items, and genotyping were approved by the Ethics Review Committee of Tsukuba International Clinical Pharmacology Clinic. A sample was collected from a sample provider who received consent by signing the consent form, and a genotype determination, a questionnaire about buckwheat, and a trait analysis by genome-wide association analysis were performed.

２．遺伝型の決定
サンプル提供の対象者から得た唾液サンプルはタカラバイオ株式会社によって処理された。
LL01及びLL02のサンプルはそれぞれ、エバージーン株式会社によって東アジア人を対象とするようにカスタムされたAxiom（登録商標）アレイ（EverGen1）によって遺伝型の決定が行われた。
このEverGen1チップは合計610093の多型を含む。そのうち569104多型は1000 Genomesプロジェクトの日本人系統サンプルにおいてMAF≧0.01を有したAxiom CHB-1チップのSNPから選ばれ、疾患上又は表現型上の既知の関連性を有する40989多型を追加したものである。
LL01及びLL02について、それぞれAffymetrix（登録商標） Analysis Suite 1.1.0616によって遺伝型データを得た。 2. Determination of genotype Saliva samples obtained from sample recipients were processed by Takara Bio Inc.
Each of the LL01 and LL02 samples was genotyped by an Axiom® array (EverGen1) customized by Evergene Corporation to target East Asians.
This EverGen1 chip contains a total of 610093 polymorphisms. Of these, 569104 polymorphism was selected from SNP of Axiom CHB-1 chip with MAF ≧ 0.01 in Japanese Genomes sample of 1000 Genomes project, and added 4089 polymorphism with known disease or phenotype association Is.
For LL01 and LL02, genotype data was obtained by Affymetrix (registered trademark) Analysis Suite 1.1.0616, respectively.

３．IBD解析によるサンプルQC
LL01及びLL02から解析対象として適したサンプルを選択した。
遺伝型データを利用して同一個体及び近縁関係にある2個体を抽出した。PLINK2 ver. 1.90p（2016年8月16日リリース）｛Purcell et al.、2007、 #42652｝を利用して、総当りの2個体のPIHAT値を算出し、0.5以上のペアを11組検出した。それぞれの11ペアについて、個体Call Rate値の悪い個体を解析対象から除外した。 3. Sample QC by IBD analysis
A sample suitable for analysis was selected from LL01 and LL02.
Using genotype data, we extracted the same individuals and two closely related individuals. PLINK2 ver. 1.90p (released on August 16, 2016) {Purcell et al., 2007, # 42652} is used to calculate the total number of PIHAT values of two individuals and detect 11 pairs of 0.5 or more pairs did. For each 11 pairs, individuals with poor individual Call Rate values were excluded from the analysis.

４．PCA解析によるサンプルQC
PCA解析を利用してLL01及びLL02から日本人由来の個体を選択した。
1000 GenomesプロジェクトのPhase 3サンプル集団から2504個体のサンプルの遺伝型データ（ftp://ftp-trace.ncbi.nih.gov/1000genomes/ftp/release/20130502/）をダウンロードし、人種の教師データとした。
教師データとLL01及びLL02の遺伝型データを結合し、PCA解析を行なった。PCA解析に利用したSNPは121595座位で、これらはPLINK2 v1.90pにより連鎖不平衡の低いSNPとして選択した。選択基準はr²<0.2とした{Purcell et al.、2007、 #42652; Chang et al.、2015、 #66208}。
第1主成分得点、第２主成分得点をそれぞれ横軸、縦軸にとった散布図を描画し、日本人教師データの近傍にあるLL01及びLL02の個体を解析対象として選択した{Yamaguchi-Kabata et al.、 2008、 #51107; Tian et al.、 2008、 #28781}。
ソバカスに関するアンケートデータと遺伝型データの両方を有するサンプルで、IBD解析及びPCA解析により解析対象として選択した個体数は、LL01が5750個体、LL02は5628個体であった。 4). Sample QC by PCA analysis
Individuals derived from Japanese were selected from LL01 and LL02 using PCA analysis.
Download genotype data (ftp://ftp-trace.ncbi.nih.gov/1000genomes/ftp/release/20130502/) of 2504 specimens from Phase 3 sample population of 1000 Genomes project, and race teacher data It was.
PCA analysis was performed by combining teacher data and genotype data of LL01 and LL02. The SNPs used for PCA analysis were at the 121595 locus, and these were selected as SNPs with low linkage disequilibrium by PLINK2 v1.90p. The selection criterion was r ² <0.2 {Purcell et al., 2007, # 42652; Chang et al., 2015, # 66208}.
Draw a scatter plot with the first and second principal component scores on the horizontal and vertical axes, respectively, and select individuals LL01 and LL02 in the vicinity of the Japanese teacher data for analysis {Yamaguchi-Kabata et al., 2008, # 51107; Tian et al., 2008, # 28781}.
In the sample having both questionnaire data and genotype data on Sobacus, the number of individuals selected as analysis targets by IBD analysis and PCA analysis was 5750 individuals for LL01 and 5628 individuals for LL02.

５．SNPのQC
LL01及びLL02それぞれの集団を対象に、解析対象SNPを選択した。選択基準は、1) SNPコールレート≧99%以上、2) MAF≧0.01、3) HWE P値≧1x10^-6とした。
さらにLL01とLL02には329個体の重複サンプルが存在する。本研究では、これら重複個体についてLL01とLL02で決定されたSNPの遺伝型の一致率を算出し、一致率が90%以上のSNPを解析対象とした。
その結果、536506個のSNPが解析対象として選択された。そのうち2417個は挿入-欠失多型（INDEL）であった。 5. SNP QC
Analysis target SNPs were selected for the respective populations of LL01 and LL02. The selection criteria were 1) SNP call rate ≧ 99%, 2) MAF ≧ 0.01, 3) HWE P value ≧ 1 × 10 ⁻⁶ .
Furthermore, there are 329 duplicate samples in LL01 and LL02. In this study, the SNP genotype match rate determined by LL01 and LL02 was calculated for these duplicate individuals, and SNPs with a match rate of 90% or more were analyzed.
As a result, 536506 SNPs were selected for analysis. Of these, 2417 were insertion-deletion polymorphisms (INDEL).

６．表現型データの処理
ソバカスの形質についてのアンケート項目は、「ソバカスができやすい」という質問に対して、「とても当てはまる」、「やや当てはまる」、「当てはまらない」の三つに選択肢から回答するものであり、「とても当てはまる」及び「やや当てはまる」と回答した場合を“ソバカスになり易い”ケースとした。 6). Processing of phenotype data Questionnaire items on the traits of buckwheat are answers to three questions: “very true”, “somewhat true”, and “not true” in response to the question “easy to do sobacus”. Yes, the cases where “very true” and “somewhat true” were answered were considered “prone to buckwheat”.

７．統計解析及び遺伝型予測
マイナーアレルに傾向性様式を仮定し、関連性の有無をロジスティック回帰分析法を用いて評価した。ソフトウェアはPLINK2 v1.90pを利用した。
１つのサンプル集団で探索解析を行ない関連候補遺伝子多型を選択し、もう1つの独立サンプルで検証解析を行った{Zeng et al., 2016, #85331}。実際にはLL01及びLL02それぞれで関連解析を実施し、一方を探索解析、もう一方を検証解析とした。
探索解析における有意水準をP_discovery≦1x10^-4とし、検証解析における有意水準をP_evaluation<0.05とした。
検証解析ではBenjamini-HochbergのFDR値による評価も行った。FDR値に対する基準はP_evaluation<0.2とした。
2つの解析結果を統合するためにオッズ比に対するメタ解析を実施した。メタ解析によるP値に対する有意水準はP_{Meta-analysis}<5x10^-8とした。 7). Statistical analysis and genotype prediction Assuming a tendency pattern for minor alleles, the presence or absence of association was evaluated using logistic regression analysis. The software used was PLINK2 v1.90p.
Search analysis was performed on one sample population, relevant candidate gene polymorphisms were selected, and validation analysis was performed on another independent sample {Zeng et al., 2016, # 85331}. Actually, LL01 and LL02 were each subjected to a related analysis, one being a search analysis and the other being a verification analysis.
The significance level in the search analysis was P _discovery ≦ 1x10 ^-4, and the significance level in the validation analysis was P _evaluation <0.05.
In the verification analysis, Benjamini-Hochberg FDR values were also evaluated. The criterion for the FDR value was P _evaluation <0.2.
A meta-analysis on the odds ratio was performed to integrate the two analysis results. The significance level for the P value by meta _-analysis was P _{Meta-analysis} <5x10 ^-8 .

８．ゲノムインピュテーションによる評価
探索解析と検証解析によって関連候補遺伝子多型を決定し、その周辺の未観測遺伝子多型の遺伝型を擬似的に推定した。先ずBEAGLE 4.1{Browning and Browning、 2007、 #74753}を用いてLL01/LL02遺伝型判定データセットをプレフェージング（pre-phasing）し、次にBEAGLE 4.1を用い、1000Genomes Phase 3の参照ハプロタイプを用いて遺伝型をインピュテーションした{Browning and Browning、 2016、 #55674}。
ゲノムインピュテーションにより擬似的に推定された遺伝型を用いて、関連解析を行った。同様にLL01及びLL02にそれぞれについて関連解析を行ない、メタ解析により2つの解析結果を統合し評価した。 8). Evaluation by genome imputation The relevant candidate gene polymorphism was determined by exploratory analysis and verification analysis, and the genotype of the unobserved gene polymorphism around it was estimated. First, pre-phasing the LL01 / LL02 genotyping dataset using BEAGLE 4.1 {Browning and Browning, 2007, # 74753}, then using BEAGLE 4.1 and the 1000 Genomes Phase 3 reference haplotype Imputed genotype {Browning and Browning, 2016, # 55674}.
Association analysis was performed using genotypes estimated by genome imputation. Similarly, LL01 and LL02 were respectively analyzed for association, and two analysis results were integrated and evaluated by meta-analysis.

９．機能解析(In Silico)
HaploReg 4.1{Ward and Kellis、2012、 #42668}を用いて多型のアノテーション付けを行った。これは、転写因子結合部位（TFBS）についての制御系アノテーション、DNase高感受性部位（DHS）、DNAメチル化、進化的な保存度のスコア（GERP）、遺伝子オーバーラップ、及びeQTL アノテーションを含むものであった。 9. Functional analysis (In Silico)
Polymorphic annotation was performed using HaploReg 4.1 {Ward and Kellis, 2012, # 42668}. This includes regulatory annotations on transcription factor binding sites (TFBS), DNase hypersensitive sites (DHS), DNA methylation, evolutionary conservation score (GERP), gene overlap, and eQTL annotations. there were.

１０．結果
上記１．〜９．の解析の結果、ヒトのソバカスになり易さを判定するために有用な遺伝子多型として、米国バイオテクノロジー情報センター（NCBI）SNPデータベースに登録されている表１〜６に示される一塩基多型を特定した。また、表７に示される挿入型多型、欠失型多型、又は塩基繰り返し多型を特定した。そして、これらの遺伝子多型を含む遺伝子、又は近傍の遺伝子としてPPARGC1B遺伝子、BNC2遺伝子、又はHSPA12A遺伝子を見出した。 10. Results Above 1. ~ 9. As a result of analysis, single nucleotide polymorphisms shown in Tables 1 to 6 registered in the US Biotechnology Information Center (NCBI) SNP database as gene polymorphisms useful for determining the likelihood of becoming human buckwheat Identified. In addition, the insertion polymorphism, deletion polymorphism, or base repeat polymorphism shown in Table 7 was identified. Then, PPARGC1B gene, BNC2 gene, or HSPA12A gene was found as a gene containing these gene polymorphisms or a nearby gene.

表１〜６に示される一塩基多型及び表７に示される挿入型多型、欠失型多型、又は塩基繰り返し多型において、リスクアレルを含む遺伝型ほど “ソバカスになり易い”と判定され得た。例えば、一塩基多型が次の１）〜２２８）に示されるものである場合は、遺伝型が次の順番で“ソバカスになり易い”と判定され得た。また、挿入型多型、欠失型多型、又は塩基繰り返し多型であれば次の１）〜２）に示される遺伝型である場合に“ソバカスになり易い”と判定され得た。さらにPPARGC1B遺伝子、BNC2遺伝子、又はHSPA12A遺伝子はソバカスの発生に関連し得る遺伝子と推定された。 In single nucleotide polymorphisms shown in Tables 1 to 6 and insertion polymorphisms, deletion polymorphisms or base repeat polymorphisms shown in Table 7, genotypes containing risk alleles are judged to be more prone to buckwheat Could have been. For example, when the single nucleotide polymorphism is one shown in the following 1) to 228), the genotype could be determined as “prone to buckwheat” in the following order. In addition, if it is an insertion type polymorphism, a deletion type polymorphism, or a base repeat polymorphism, the genotype shown in the following 1) to 2) can be determined to be “prone to buckwheat”. Furthermore, the PPARGC1B gene, the BNC2 gene, or the HSPA12A gene was presumed to be a gene that can be related to the development of buckwheat.

＜一塩基多型＞
１）rs75548653のアレルCを保有する遺伝型、２）rs79694606のアレルGを保有する遺伝型、３）rs79489540のアレルCを保有する遺伝型、４）rs4235745のアレルCを保有する遺伝型、５）rs78814834のアレルCを保有する遺伝型、６）rs4705384のアレルTを保有する遺伝型、７）rs67393352のアレルGを保有する遺伝型、８）rs17110447のアレルAを保有する遺伝型、９）rs77655035のアレルCを保有する遺伝型、１０）rs251468のアレルCを保有する遺伝型、１１）rs80069564のアレルGを保有する遺伝型、１２）rs109075のアレルTを保有する遺伝型、１３）rs109076のアレルTを保有する遺伝型、１４）rs251467のアレルTを保有する遺伝型、１５）rs251466のアレルCを保有する遺伝型、１６）rs17110463のアレルCを保有する遺伝型、１７）rs251465のアレルAを保有する遺伝型、１８）rs251464のアレルGを保有する遺伝型、１９）rs251463のアレルGを保有する遺伝型、２０）rs251462のアレルAを保有する遺伝型、２１）rs4705385のアレルCを保有する遺伝型、２２）rs109077のアレルTを保有する遺伝型、２３）rs112183859のアレルAを保有する遺伝型、２４）rs251460のアレルTを保有する遺伝型、２５）rs76390604のアレルTを保有する遺伝型、２６）rs17600568のアレルCを保有する遺伝型、２７）rs10491360のアレルTを保有する遺伝型、２８）rs251459のアレルGを保有する遺伝型、２９）rs79435714のアレルCを保有する遺伝型、３０）rs32589のアレルGを保有する遺伝型、３１）rs32588のアレルTを保有する遺伝型、３２）rs32587のアレルTを保有する遺伝型、３３）rs32586のアレルAを保有する遺伝型、３４）rs2003602のアレルGを保有する遺伝型、３５）rs32585のアレルAを保有する遺伝型、３６）rs28282のアレルCを保有する遺伝型、３７）rs17653577のアレルAを保有する遺伝型、３８）rs32584のアレルAを保有する遺伝型、３９）rs32583のアレルCを保有する遺伝型、４０）rs17110586のアレルCを保有する遺伝型、４１）rs32581のアレルGを保有する遺伝型、４２）rs45560442のアレルGを保有する遺伝型、４３）rs76994147のアレルGを保有する遺伝型、４４）rs45520937のアレルGを保有する遺伝型、４５）rs45588534のアレルCを保有する遺伝型、４６）rs45543631のアレルCを保有する遺伝型、４７）rs75739000のアレルGを保有する遺伝型、４８）rs6579761のアレルGを保有する遺伝型、４９）rs1549186のアレルTを保有する遺伝型、５０）rs1549187のアレルCを保有する遺伝型、５１）rs1549188のアレルAを保有する遺伝型、５２）rs26122のアレルCを保有する遺伝型、５３）rs1107344のアレルGを保有する遺伝型、５４）rs2341294のアレルGを保有する遺伝型、５５）rs888853のアレルAを保有する遺伝型、５６）rs7712296のアレルCを保有する遺伝型、５７）rs17653703のアレルCを保有する遺伝型、５８）rs10756813のアレルCを保有する遺伝型、５９）rs10756814のアレルAを保有する遺伝型、６０）rs76211545のアレルGを保有する遺伝型、６１）rs74645810のアレルTを保有する遺伝型、６２）rs76233908のアレルAを保有する遺伝型、６３）rs12376135のアレルAを保有する遺伝型、６４）rs10810635のアレルCを保有する遺伝型、６５）rs16935073のアレルCを保有する遺伝型、６６）rs10962601のアレルGを保有する遺伝型、６７）rs10962609のアレルCを保有する遺伝型、６８）rs4455968のアレルTを保有する遺伝型、６９）rs4523356のアレルAを保有する遺伝型、７０）rs12351269のアレルCを保有する遺伝型、７１）rs10121347のアレルCを保有する遺伝型、７２）rs10122901のアレルGを保有する遺伝型、７３）rs2921966のアレルTを保有する遺伝型、７４）rs3010462のアレルAを保有する遺伝型、７５）rs3010463のアレルAを保有する遺伝型、７６）rs1900500のアレルTを保有する遺伝型、７７）rs2921967のアレルGを保有する遺伝型、７８）rs2921968のアレルAを保有する遺伝型、７９）rs2907238のアレルAを保有する遺伝型、８０）rs2907237のアレルCを保有する遺伝型、８１）rs2921969のアレルTを保有する遺伝型、８２）rs7902159のアレルGを保有する遺伝型、８３）rs7902262のアレルTを保有する遺伝型、８４）rs3010464のアレルAを保有する遺伝型、８５）rs1076369のアレルAを保有する遺伝型、８６）rs1076368のアレルTを保有する遺伝型、８７）rs1076367のアレルGを保有する遺伝型、８８）rs740595のアレルCを保有する遺伝型、８９）rs733216のアレルGを保有する遺伝型、９０）rs2240711のアレルTを保有する遺伝型、９１）rs2240710のアレルGを保有する遺伝型、９２）rs2921971のアレルTを保有する遺伝型、９３）rs12263233のアレルCを保有する遺伝型、９４）rs3010467のアレルCを保有する遺伝型、９５）rs12265205のアレルCを保有する遺伝型、９６）rs2907231のアレルCを保有する遺伝型、９７）rs3010468のアレルGを保有する遺伝型、９８）rs2921972のアレルAを保有する遺伝型、９９）rs3010469のアレルCを保有する遺伝型、１００）rs3010470のアレルCを保有する遺伝型、１０１）rs12259725のアレルTを保有する遺伝型、１０２）rs12259865のアレルAを保有する遺伝型、１０３）rs71500866のアレルAを保有する遺伝型、１０４）rs12259866のアレルAを保有する遺伝型、１０５）rs12259830のアレルTを保有する遺伝型、１０６）rs12259842のアレルTを保有する遺伝型、１０７）rs12245201のアレルGを保有する遺伝型、１０８）rs12782444のアレルTを保有する遺伝型、１０９）rs3010471のアレルCを保有する遺伝型、１１０）rs2921973のアレルTを保有する遺伝型、１１１）rs3010475のアレルGを保有する遺伝型、１１２）rs3010476のアレルAを保有する遺伝型、１１３）rs3010477のアレルGを保有する遺伝型、１１４）rs2907230のアレルTを保有する遺伝型、１１５）rs3010478のアレルGを保有する遺伝型、１１６）rs3010479のアレルCを保有する遺伝型、１１７）rs3010480のアレルCを保有する遺伝型、１１８）rs3010481のアレルCを保有する遺伝型、１１９）rs2901119のアレルCを保有する遺伝型、１２０）rs2420327のアレルCを保有する遺伝型、１２１）rs3010484のアレルAを保有する遺伝型、１２２）rs2907229のアレルTを保有する遺伝型、１２３）rs2420328のアレルCを保有する遺伝型、１２４）rs2420329のアレルAを保有する遺伝型、１２５）rs2901120のアレルGを保有する遺伝型、１２６）rs3010488のアレルTを保有する遺伝型、１２７）rs3010489のアレルAを保有する遺伝型、１２８）rs2240709のアレルAを保有する遺伝型、１２９）rs2240708のアレルGを保有する遺伝型、１３０）rs2907241のアレルTを保有する遺伝型、１３１）rs2921974のアレルGを保有する遺伝型、１３２）rs12245621のアレルCを保有する遺伝型、１３３）rs2921975のアレルGを保有する遺伝型、１３４）rs2921976のアレルAを保有する遺伝型、１３５）rs3010491のアレルTを保有する遺伝型、１３６）rs77204400のアレルGを保有する遺伝型、１３７）rs1638429のアレルTを保有する遺伝型、１３８）rs758368のアレルAを保有する遺伝型、１３９）rs4752110のアレルTを保有する遺伝型、１４０）rs7070575のアレルCを保有する遺伝型、１４１）rs12146158のアレルCを保有する遺伝型、１４２）rs10444110のアレルTを保有する遺伝型、１４３）rs11198112のアレルCを保有する遺伝型、１４４）rs10444039のアレルCを保有する遺伝型、１４５）rs17096846のアレルAを保有する遺伝型、１４６）rs1925257のアレルAを保有する遺伝型、１４７）rs1925258のアレルTを保有する遺伝型、１４８）rs55927713のアレルTを保有する遺伝型、１４９）rs35563099のアレルCを保有する遺伝型、１５０）rs7098111のアレルCを保有する遺伝型、１５１）rs7074192のアレルGを保有する遺伝型、１５２）rs12773211のアレルCを保有する遺伝型、１５３）rs555269109のアレルGを保有する遺伝型、１５４）rs532411111のアレルGを保有する遺伝型、１５５）rs4994045のアレルCを保有する遺伝型、１５６）rs10886144のアレルAを保有する遺伝型、１５７）rs34878973のアレルGを保有する遺伝型、１５８）rs10886148のアレルGを保有する遺伝型、１５９）rs4752116のアレルCを保有する遺伝型、１６０）rs12241016のアレルCを保有する遺伝型、１６１）rs11198128のアレルAを保有する遺伝型、１６２）rs10787798のアレルCを保有する遺伝型、１６３）rs10749251のアレルTを保有する遺伝型、１６４）rs6585463のアレルAを保有する遺伝型、１６５）rs1925262のアレルGを保有する遺伝型、１６６）rs4752117のアレルCを保有する遺伝型、１６７）rs10749252のアレルAを保有する遺伝型、１６８）rs7085292のアレルCを保有する遺伝型、１６９）rs4431946のアレルCを保有する遺伝型、１７０）rs4752118のアレルCを保有する遺伝型、
１７１）rs4752119のアレルAを保有する遺伝型、１７２）rs10749253のアレルGを保有する遺伝型、１７３）rs4752120のアレルTを保有する遺伝型、１７４）rs4751641のアレルGを保有する遺伝型、１７５）rs10787799のアレルGを保有する遺伝型、１７６）rs10886150のアレルCを保有する遺伝型、１７７）rs11198135のアレルCを保有する遺伝型、１７８）rs10886151のアレルGを保有する遺伝型、１７９）rs1925264のアレルCを保有する遺伝型、１８０）rs4752122のアレルAを保有する遺伝型、１８１）rs11498896のアレルGを保有する遺伝型、１８２）rs199983705のアレルTを保有する遺伝型、１８３）rs11198141のアレルTを保有する遺伝型、１８４）rs2094020のアレルGを保有する遺伝型、１８５）rs10787800のアレルCを保有する遺伝型、１８６）rs7098136のアレルTを保有する遺伝型、１８７）rs12250372のアレルGを保有する遺伝型、１８８）rs7916406のアレルGを保有する遺伝型、１８９）rs61866017のアレルGを保有する遺伝型、１９０）rs12103642のアレルAを保有する遺伝型、１９１）rs8066617のアレルAを保有する遺伝型、１９２）rs12942131のアレルTを保有する遺伝型、１９３）rs10515135のアレルCを保有する遺伝型、１９４）rs8078098のアレルGを保有する遺伝型、１９５）rs916815のアレルCを保有する遺伝型、１９６）rs8076498のアレルTを保有する遺伝型、１９７）rs59521320のアレルCを保有する遺伝型、１９８）rs72828937のアレルCを保有する遺伝型、１９９）rs62060342のアレルCを保有する遺伝型、２００）rs62060343のアレルGを保有する遺伝型、２０１）rs1016984のアレルTを保有する遺伝型、２０２）rs1016985のアレルTを保有する遺伝型、２０３）rs1016986のアレルGを保有する遺伝型、２０４）rs1016987のアレルCを保有する遺伝型、２０５）rs17220593のアレルAを保有する遺伝型、２０６）rs17821090のアレルCを保有する遺伝型、２０７）rs4794701のアレルGを保有する遺伝型、２０８）rs4794702のアレルCを保有する遺伝型、２０９）rs8064252のアレルTを保有する遺伝型、２１０）rs17220607のアレルTを保有する遺伝型、２１１）rs8081915のアレルGを保有する遺伝型、２１２）rs4794703のアレルGを保有する遺伝型、２１３）rs4452017のアレルTを保有する遺伝型、２１４）rs4284702のアレルAを保有する遺伝型、２１５）rs8067946のアレルAを保有する遺伝型、２１６）rs34773938のアレルGを保有する遺伝型、２１７）rs17220621のアレルGを保有する遺伝型、２１８）rs35479111のアレルGを保有する遺伝型、２１９）rs62060346のアレルCを保有する遺伝型、２２０）rs62060347のアレルTを保有する遺伝型、２２１）rs62060348のアレルGを保有する遺伝型、２２２）rs17833789のアレルCを保有する遺伝型、２２３）rs9907841のアレルGを保有する遺伝型、２２４）rs62060349のアレルTを保有する遺伝型、２２５）rs11079281のアレルTを保有する遺伝型、２２６）rs17821126のアレルGを保有する遺伝型、２２７）rs80243896のアレルCを保有する遺伝型、２２８）rs59704173のアレルAを保有する遺伝型 <Single nucleotide polymorphism>
1) genotype possessing allele C of rs75548653, 2) genotype possessing allele G of rs79694606, 3) genotype possessing allele C of rs79489540, 4) genotype possessing allele C of rs4235745, 5) genotype possessing allele C of rs78814834, 6) genotype possessing allele T of rs4705384, 7) genotype possessing allele G of rs67393352, 8) genotype possessing allele A of rs17110447, 9) genotype possessing allele A of rs17110447 Genotype with allele C, 10) genotype with allele C of rs251468, 11) genotype with allele G of rs80069564, 12) genotype with allele T of rs109075, 13) allele T of rs109076 14) genotype with rs251467 allele T, 15) genotype with rs251466 allele C, 16) genotype with rs17110463 allele C, 17) rs251465 allele A 18) Keep allele G of rs251464 19) genotype possessing allele G of rs251463, 20) genotype possessing allele A of rs251462, 21) genotype possessing allele C of rs4705385, 22) inheritance possessing allele T of rs109077 23) genotype possessing allele A of rs112183859, 24) genotype possessing allele T of rs251460, 25) genotype possessing allele T of rs76390604, 26) genotype possessing allele C of rs17600568, 27) genotype possessing allele T of rs10491360, 28) genotype possessing allele G of rs251459, 29) genotype possessing allele C of rs79435714, 30) genotype possessing allele G of rs32589, 31) genotype possessing allele T of rs32588, 32) genotype possessing allele T of rs32587, 33) genotype possessing allele A of rs32586, 34) genotype possessing allele G of rs2003602, 35) genotype possessing allele G of rs2003602 Genotype with allele A, 3 ) Genotype possessing allele C of rs28282, 37) genotype possessing allele A of rs17653577, 38) genotype possessing allele A of rs32584, 39) genotype possessing allele C of rs32583, 40) rs17110586 Genotype with allele C of 41, genotype with allele G of rs32581, 42) genotype with allele G of rs45560442, 43) genotype with allele G of rs76994147, 44) allele of rs45520937 Genotype with G, 45) genotype with rs45588534 allele C, 46) genotype with rs45543631 allele C, 47) genotype with rs75739000 allele G, 48) allele G with rs6579761 Genotype possessed, 49) genotype possessing allele T of rs1549186, 50) genotype possessing allele C of rs1549187, 51) genotype possessing allele A of rs1549188, 52) possessing allele C of rs26122 Genotype, 53) rs1107344 Genotype possessing allele G, 54) genotype possessing allele G of rs2341294, 55) genotype possessing allele A of rs888853, 56) genotype possessing allele C of rs7712296, 57) allele C of rs17653703 58) genotype possessing allele C of rs10756813, 59) genotype possessing allele A of rs10756814, 60) genotype possessing allele G of rs76211545, 61) possessing allele T of rs74645810 62) genotype possessing allele A of rs76233908, 63) genotype possessing allele A of rs12376135, 64) genotype possessing allele C of rs10810635, 65) inheritance possessing allele C of rs16935073 66) genotype possessing allele G of rs10962601, 67) genotype possessing allele C of rs10962609, 68) genotype possessing allele T of rs4455968, 69) genotype possessing allele A of rs4523356, 70) rs12351269 Genotype possessing allele C, 71) genotype possessing allele C of rs10121347, 72) genotype possessing allele G of rs10122901, 73) genotype possessing allele T of rs2921966, 74) allele A of rs3010462 75) genotype possessing allele A of rs3010463, 76) genotype possessing allele T of rs1900500, 77) genotype possessing allele G of rs2921967, 78) possessing allele A of rs2921968 79) genotype possessing allele A of rs2907238, 80) genotype possessing allele C of rs2907237, 81) genotype possessing allele T of rs2921969, 82) inheritance possessing allele G of rs7902159 83) genotype possessing allele T of rs7902262, 84) genotype possessing allele A of rs3010464, 85) genotype possessing allele A of rs1076369, 86) genotype possessing allele T of rs1076368, 87) Allele G of rs1076367 88) genotype possessing allele C of rs740595, 89) genotype possessing allele G of rs733216, 90) genotype possessing allele T of rs2240711, 91) inheritance possessing allele G of rs2240710 92) genotype possessing allele C of rs2921971, 93) genotype possessing allele C of rs12263233, 94) genotype possessing allele C of rs3010467, 95) genotype possessing allele C of rs12265205, 96) genotype possessing allele C of rs2907231, 97) genotype possessing allele G of rs3010468, 98) genotype possessing allele A of rs2921972, 99) genotype possessing allele C of rs3010469, 100) genotype possessing allele C of rs3010470, 101) genotype possessing allele T of rs12259725, 102) genotype possessing allele A of rs12259865, 103) genotype possessing allele A of rs71500866, 104) genotype possessing allele A of rs71500866 Allele Genotype possessing A, 105) genotype possessing allele T of rs12259830, 106) genotype possessing allele T of rs12259842, 107) genotype possessing allele G of rs12245201, 108) allele T of rs12782444 109) genotype possessing allele C of rs3010471, 110) genotype possessing allele T of rs2921973, 111) genotype possessing allele G of rs3010475, 112) possessing allele A of rs3010476 Genotype, 113) genotype possessing allele G of rs3010477, 114) genotype possessing allele T of rs2907230, 115) genotype possessing allele G of rs3010478, 116) genotype possessing allele C of rs3010479 117) genotype possessing allele C of rs3010480, 118) genotype possessing allele C of rs3010481, 119) genotype possessing allele C of rs2901119, 120) remnant possessing allele C of rs2420327 121) genotype possessing allele A of rs3010484, 122) genotype possessing allele T of rs2907229, 123) genotype possessing allele C of rs2420328, 124) genotype possessing allele A of rs2420329, 125) genotype possessing allele G of rs2901120, 126) genotype possessing allele T of rs3010488, 127) genotype possessing allele A of rs3010489, 128) genotype possessing allele A of rs2240709, 129) genotype possessing allele G of rs2240708, 130) genotype possessing allele T of rs2907241, 131) genotype possessing allele G of rs2921974, 132) genotype possessing allele C of rs12245621, 133) of genotype possessing allele C Genotype possessing allele G, 134) genotype possessing allele A of rs2921976, 135) genotype possessing allele T of rs3010491, 136) genotype possessing allele G of rs77204400, 137) rs Genotype with allele T of 1638429, 138) genotype with allele A of rs758368, 139) genotype with allele T of rs4752110, 140) genotype with allele C of rs7070575, 141) rs12146158 of genotype Genotype with allele C, 142) genotype with allele T of rs10444110, 143) genotype with allele C of rs11198112, 144) genotype with allele C of rs10444039, 145) allele A of rs17096846 146) genotype possessing allele T of rs1925257, 147) genotype possessing allele T of rs1925258, 148) genotype possessing allele T of rs55927713, 149) possessing allele C of rs35563099 150) genotype possessing allele C of rs7098111, 151) genotype possessing allele G of rs7074192, 152) genotype possessing allele C of rs12773211, 153) allele of rs555269109 Genotype possessing allele G of 154) genotype possessing allele G of rs532411111, 155) genotype possessing allele C of rs4994045, 156) genotype possessing allele A of rs10886144, 157) allele G of rs34878973 158) genotype possessing allele G of rs10886148, 159) genotype possessing allele C of rs4752116, 160) genotype possessing allele C of rs12241016, 161) possessing allele A of rs11198128 162) genotype with allele C of rs10787798, 163) genotype with allele T of rs10749251, 164) genotype with allele A of rs6585463, 165) heredity with allele G of rs1925262 166) genotype with rs4752117 allele C, 167) genotype with rs10749252 allele A, 168) genotype with rs7085292 allele C, 169) rs4431946 with allele C 170) genotype possessing allele C of rs4752118,
171) genotype possessing allele A of rs4752119, 172) genotype possessing allele G of rs10749253, 173) genotype possessing allele T of rs4752120, 174) genotype possessing allele G of rs4751641, 175) genotype possessing allele G of rs10787799, 176) genotype possessing allele C of rs10886150, 177) genotype possessing allele C of rs11198135, 178) genotype possessing allele G of rs10886151, 179) Genotype with allele C, 180) genotype with allele A of rs4752122, 181) genotype with allele G of rs11498896, 182) genotype with allele T of rs199983705, 183) allele T of rs11198141 184) genotype possessing allele G of rs2094020, 185) genotype possessing allele C of rs10787800, 186) genotype possessing allele T of rs7098136, 187) rs Genotype with allele G of 12250372, 188) genotype with allele G of rs7916406, 189) genotype with allele G of rs61866017, 190) genotype with allele A of rs12103642, 191) rs8066617 Genotype with allele A, 192) genotype with allele T of rs12942131, 193) genotype with allele C of rs10515135, 194) genotype with allele G of rs8078098, 195) allele C of rs916815 196) genotype possessing allele C of rs8076498, 197) genotype possessing allele C of rs59521320, 198) genotype possessing allele C of rs72828937, 199) possessing allele C of rs62060342 200) genotype possessing allele T of rs62060343, 201) genotype possessing allele T of rs1016984, 202) genotype possessing allele T of rs1016985, 203) array of rs1016986 204) genotype with allele C of rs1016987, 205) genotype with allele A of rs17220593, 206) genotype with allele C of rs17821090, 207) allele G of rs4794701 208) genotype with rs4794702 allele C, 209) genotype with rs8064252 allele T, 210) genotype with rs17220607 allele T, 211) rs8081915 with allele G 212) genotype possessing allele G of rs4794703, 213) genotype possessing allele T of rs4452017, 214) genotype possessing allele A of rs4284702, 215) inheritance possessing allele A of rs8067946 216) genotype possessing allele G of rs34773938, 217) genotype possessing allele G of rs17220621, 218) genotype possessing allele G of rs35479111, 219) possessing allele C of rs62060346 Genotype, 220) genotype possessing allele T of rs62060347, 221) genotype possessing allele G of rs62060348, 222) genotype possessing allele C of rs17833789, 223) genotype possessing allele G of rs9907841 224) genotype possessing allele T of rs62060349, 225) genotype possessing allele T of rs11079281, 226) genotype possessing allele G of rs17821126, 227) genotype possessing allele C of rs80243896, 228 ) Genotype carrying allele A of rs59704173

＜挿入型多型、欠失型多型、又は塩基繰り返し多型＞
１）rs140364236のアレルATAAGGを保有する遺伝子型、２）rs77002482のアレルCAAを保有する遺伝子型、３）rs5872148のアレルTを保有する遺伝子型、４）rs143978112のアレルTを保有する遺伝子型、５）rs67920508のアレルCを保有する遺伝子型、６）rs11413212のアレルATを保有する遺伝子型、７）rs67892375のアレルAを保有する遺伝子型、８）rs5788185のアレルATを保有する遺伝子型、９）rs36103789のアレルGAを保有する遺伝子型、１０）rs35271333のアレルTを保有する遺伝子型、１１）rs34828951のアレルAを保有する遺伝子型、１２）rs10647236のアレルCを保有する遺伝子型、１３）rs148896299のアレルGTTTAを保有する遺伝子型、１４）rs11436341のアレルAを保有する遺伝子型、１５）rs5821164のアレルCTを保有する遺伝子型、１６）rs112409672のアレルTAを保有する遺伝子型、１７）rs111581498のアレルACを保有する遺伝子型、１８）rs145273475のアレルCCCAGCACTTTAGGAGGCTGAGGを保有する遺伝子型、１９）rs530322916のアレルCを保有する遺伝子型、２０）rs200262366のアレルCAAを保有する遺伝子型、２１）rs548590979のアレルATを保有する遺伝子型 <Insertion polymorphism, deletion polymorphism, or base repeat polymorphism>
1) Genotype possessing allele ATAAGG of rs140364236, 2) Genotype possessing allele CAA of rs77002482, 3) Genotype possessing allele T of rs5872148, 4) Genotype possessing allele T of rs143978112, 5) genotype possessing allele C of rs67920508, 6) genotype possessing allele AT of rs11413212, 7) genotype possessing allele A of rs67892375, 8) genotype possessing allele AT of rs5788185, 9) genotype possessing allele AT of rs5788185, 9) Genotype possessing allele GA, 10) genotype possessing allele T of rs35271333, 11) genotype possessing allele A of rs34828951, 12) genotype possessing allele C of rs10647236, 13) allele GTTTA of rs148896299 14) genotype possessing allele A of rs11436341, 15) genotype possessing allele CT of rs5821164, 16) genotype possessing allele TA of rs112409672, 17) rs1115814 Genotype possessing 98 alleles AC, 18) genotype possessing alleles CCCAGCACTTTAGGAGGCTGAGG of rs145273475, 19) genotype possessing allele C of rs530322916, 20) genotype possessing allele CAA of rs200262366, 21) rs548590979 Genotype possessing allele AT

本発明の方法により、対象となるヒトそれぞれのソバカスになり易さを網羅的に把握することができる。また、判定用ポリヌクレオチドや判定用キットの使用により、ソバカスになり易さを簡便に把握することも可能となる。
さらに、本発明によりソバカスに関連する遺伝子の発現等を制御することでソバカスの予防又は治療のための組成物を提供することも可能となる。 By the method of the present invention, it is possible to comprehensively grasp the easiness of becoming a target of each target human. In addition, by using the determination polynucleotide or the determination kit, it is possible to easily grasp the easiness of becoming buckwheat.
Furthermore, the present invention can provide a composition for preventing or treating buckwheat by controlling the expression of genes related to buckwheat.

Claims

A method for determining the likelihood of a subject to become a buckwheat that includes a step of detecting a genetic polymorphism in a DNA-containing sample derived from a subject, and the genetic polymorphism to be detected is registered in the National Center for Biotechnology Information (NCBI) SNP database. One or more single nucleotide polymorphisms selected from the group shown in Tables 1 to 7 and / or single nucleotide polymorphisms, insertion polymorphisms, deletion polymorphisms in linkage disequilibrium with the single nucleotide polymorphisms The method of determining the ease of becoming a test subject's buckwheat which is a base repetition polymorphism.

A method for determining the likelihood of becoming a subject's buckwheat comprising a step of detecting a single nucleotide polymorphism in a DNA-containing sample derived from a subject, wherein the single nucleotide polymorphism to be detected is rs75548653, rs79694606, rs79489540, rs4235745, rs78814834, rs4705384, rs67393352, rs17110447, rs77655035, rs251468, rs80069564, rs109075, rs109076, rs251467, rs251466, rs17110463, rs251465, rs251464, rs251463, rs251462, rs4705385, rs109077, 358, rs25146014, rs25146014 rs32589, rs32588, rs32587, rs32586, rs2003602, rs32585, rs28282, rs17653577, rs32584, rs32583, rs17110586, rs32581, rs45560442, rs76994147, rs45520937, rs45588534, rs45543631, rs75739000, rs6579761, rs1549186, rs118887 rs888853, rs7712296, rs17653703, rs10756813, rs10756814, rs76211545, rs74645810, rs76233908, rs12376135, rs10810635, rs16935073, rs10962601, r s10962609, rs4455968, rs4523356, rs12351269, rs10121347, rs10122901, rs2921966, rs3010462, rs3010463, rs1900500, rs2921967, rs2921968, rs2907238, rs2907237, rs2921969, rs7902159, rs79022610, rs76, rs1076369, rs76 rs2921971, rs12263233, rs3010467, rs12265205, rs2907231, rs3010468, rs2921972, rs3010469, rs3010470, rs12259725, rs12259865, rs71500866, rs12259866, rs12259830, rs12259842, rs12245201, rs12782444, rs3010476, rs2921973, rs3010475, rs2921973, rs3010475 rs3010480, rs3010481, rs2901119, rs2420327, rs3010484, rs2907229, rs2420328, rs2420329, rs2901120, rs3010488, rs3010489, rs2240709, rs2240708, rs2907241, rs2921974, rs12245621, rs2921975, rs2921976, rs3010491, rs77400, rs3010491, rs77400 rs10444110, rs11198112, rs10444039, rs17096846, rs1925257, rs1925258, rs55927713 rs35563099, rs7098111, rs7074192, rs12773211, rs555269109, rs532411111, rs4994045, rs10886144, rs34878973, rs10886148, rs4752116, rs12241016, rs11198128, rs10787798, rs10749251, rs6585463, rs1925262, 475, rs107, rs10749252, rs1074 rs4751641, rs10787799, rs10886150, rs11198135, rs10886151, rs1925264, rs4752122, rs11498896, rs199983705, rs11198141, rs2094020, rs10787800, rs7098136, rs12250372, rs7916406, rs61866017, rs12103642, rs15815, rs1294298 rs62060342, rs62060343, rs1016984, rs1016985, rs1016986, rs1016987, rs17220593, rs17821090, rs4794701, rs4794702, rs8064252, rs17220607, rs8081915, rs4794703, rs4452017, rs4284702, rs8067946, rs347111337, rs rs62060349, rs11079281, rs17821126, rs80243896 and r The method according to claim 1, which is one or more single nucleotide polymorphisms selected from the group consisting of s59704173 and / or a single nucleotide polymorphism in linkage disequilibrium with the single nucleotide polymorphism.

genotype with allele C of rs75548653,
genotype possessing allele G of rs79694606,
genotype with allele C of rs79489540,
genotype carrying allele C of rs4235745,
genotype carrying allele C of rs78814834,
genotype carrying allele T of rs4705384,
genotype with allele G of rs67393352,
genotype carrying allele A of rs17110447,
genotype with allele C of rs77655035,
genotype with allele C of rs251468,
genotype with allele G of rs80069564,
genotype carrying allele T of rs109075,
genotype carrying allele T of rs109076,
genotype with allelic T of rs251467,
genotype carrying allele C of rs251466,
genotype with allele C of rs17110463,
genotype with allele A of rs251465,
genotype carrying allele G of rs251464,
genotype carrying allele G of rs251463,
genotype carrying allele A of rs251462,
genotype possessing allele C of rs4705385,
genotype carrying allele T of rs109077,
genotype carrying allele A of rs112183859,
genotype carrying allele T of rs251460,
genotype carrying allele T of rs76390604,
genotype with allele C of rs17600568,
genotype with allele T of rs10491360,
genotype carrying allele G of rs251459,
genotype carrying allele C of rs79435714,
genotype with allele G of rs32589,
genotype carrying allele T of rs32588,
genotype carrying allele T of rs32587,
genotype carrying allele A of rs32586,
genotype possessing allele G of rs2003602,
genotype with allele A of rs32585,
genotype carrying allele C of rs28282,
genotype with allele A of rs17653577,
genotype carrying allele A of rs32584,
genotype carrying allele C of rs32583,
genotype carrying allele C of rs17110586,
genotype carrying allele G of rs32581,
genotype with allele G of rs45560442,
genotype with allele G of rs76994147,
genotype carrying allele G of rs45520937,
genotype with allele C of rs45588534,
genotype with allele C of rs45543631,
A genotype with allele G of rs75739000,
genotype with allele G of rs6579761,
genotype carrying allele T of rs1549186,
genotype carrying allele C of rs1549187,
genotype carrying allele A of rs1549188,
genotype carrying allele C of rs26122,
genotype carrying allele G of rs1107344,
genotype carrying allele G of rs2341294,
genotype carrying allele A of rs888853,
genotype carrying allele C of rs7712296,
genotype carrying allele C of rs17653703,
genotype carrying allele C of rs10756813,
genotype carrying allele A of rs10756814,
genotype carrying allele G of rs76211545,
genotype carrying allele T of rs74645810,
genotype carrying allele A of rs76233908,
genotype carrying allele A of rs12376135,
genotype with allele C of rs10810635,
genotype carrying allele C of rs16935073,
genotype possessing allele G of rs10962601,
genotype with allele C of rs10962609,
genotype with allele T of rs4455968,
genotype with allele A of rs4523356,
genotype carrying allele C of rs12351269,
genotype carrying allele C of rs10121347,
genotype with allele G of rs10122901,
genotype carrying allele T of rs2921966,
genotype carrying allele A of rs3010462,
genotype carrying allele A of rs3010463,
genotype with allele T of rs1900500,
genotype with allele G of rs2921967,
genotype carrying allele A of rs2921968,
genotype carrying allele A of rs2907238,
genotype with allele C of rs2907237,
genotype with allele T of rs2921969,
genotype with allele G of rs7902159,
genotype carrying allele T of rs7902262,
genotype carrying allele A of rs3010464,
genotype carrying allele A of rs1076369,
genotype carrying allele T of rs1076368,
genotype possessing allele G of rs1076367,
genotype with allele C of rs740595,
genotype carrying allele G of rs733216,
genotype carrying allele T of rs2240711,
genotype carrying allele G of rs2240710,
genotype carrying allele T of rs2921971,
genotype carrying allele C of rs12263233,
genotype with allele C of rs3010467,
genotype carrying allele C of rs12265205,
genotype with allele C of rs2907231,
genotype with allele G of rs3010468,
genotype with allele A of rs2921972,
genotype with allele C of rs3010469,
genotype with allele C of rs3010470,
genotype with allele T of rs12259725,
genotype with allele A of rs12259865,
genotype with allele A of rs71500866,
genotype carrying allele A of rs12259866,
genotype with allelic T of rs12259830,
genotype with allele T of rs12259842,
genotype possessing allele G of rs12245201,
genotype with allele T of rs12782444,
genotype with allele C of rs3010471,
genotype carrying allele T of rs2921973,
genotype carrying allele G of rs3010475,
genotype carrying allele A of rs3010476,
genotype carrying allele G of rs3010477,
genotype carrying allele T of rs2907230,
genotype carrying allele G of rs3010478,
genotype with allele C of rs3010479,
genotype with allele C of rs3010480,
genotype carrying allele C of rs3010481,
genotype carrying allele C of rs2901119,
genotype carrying allele C of rs2420327,
genotype carrying allele A of rs3010484,
genotype carrying allele T of rs2907229,
genotype with allele C of rs2420328,
genotype carrying allele A of rs2420329,
genotype with allele G of rs2901120,
genotype carrying allele T of rs3010488,
genotype carrying allele A of rs3010489,
genotype with allele A of rs2240709,
genotype with allele G of rs2240708,
genotype carrying allele T of rs2907241,
genotype with allele G of rs2921974,
genotype with allele C of rs12245621,
genotype possessing allele G of rs2921975,
genotype with allele A of rs2921976,
genotype carrying allele T of rs3010491,
genotype with allele G of rs77204400,
genotype carrying allele T of rs1638429,
genotype with allele A of rs758368,
genotype carrying allele T of rs4752110,
genotype with allele C of rs7070575,
genotype carrying allele C of rs12146158,
genotype with allele T of rs10444110,
genotype with allele C of rs11198112,
genotype with allele C of rs10444039,
genotype with allele A of rs17096846,
genotype carrying allele A of rs1925257,
genotype carrying allele T of rs1925258,
genotype carrying allele T of rs55927713,
genotype with allele C of rs35563099,
genotype with allele C of rs7098111,
genotype with allele G of rs7074192,
genotype with allele C of rs12773211,
genotype carrying allele G of rs555269109,
genotype possessing allele G of rs532411111,
genotype with allele C of rs4994045,
genotype with allele A of rs10886144,
genotype carrying allele G of rs34878973,
genotype with allele G of rs10886148,
genotype carrying allele C of rs4752116,
genotype with allele C of rs12241016,
genotype possessing allele A of rs11198128,
genotype possessing allele C of rs10787798,
genotype carrying allele T of rs10749251,
genotype carrying allele A of rs6585463,
genotype with allele G of rs1925262,
genotype with allele C of rs4752117,
genotype with allele A of rs10749252,
genotype carrying allele C of rs7085292,
genotype possessing allele C of rs4431946,
genotype with allele C of rs4752118,
genotype carrying allele A of rs4752119,
genotype carrying allele G of rs10749253,
genotype with allele T of rs4752120,
genotype carrying allele G of rs4751641,
genotype possessing allele G of rs10787799,
genotype with allele C of rs10886150,
genotype with allele C of rs11198135,
genotype carrying allele G of rs10886151,
genotype carrying allele C of rs1925264,
genotype carrying allele A of rs4752122,
genotype with allele G of rs11498896,
genotype carrying allele T of rs199983705,
genotype carrying allele T of rs11198141,
genotype possessing allele G of rs2094020,
genotype with allele C of rs10787800,
genotype carrying allele T of rs7098136,
genotype carrying allele G of rs12250372,
genotype possessing allele G of rs7916406,
genotype possessing allele G of rs61866017,
genotype carrying allele A of rs12103642,
genotype carrying allele A of rs8066617,
genotype carrying allele T of rs12942131,
genotype with allele C of rs10515135,
genotype with allele G of rs8078098,
A genotype carrying allele C of rs916815,
genotype with allele T of rs8076498,
genotype with allele C of rs59521320,
genotype carrying allele C of rs72828937,
genotype with allele C of rs62060342,
genotype with allele G of rs62060343,
genotype carrying allele T of rs1016984,
genotype carrying allele T of rs1016985,
genotype carrying allele G of rs1016986,
genotype carrying allele C of rs1016987,
genotype with allele A of rs17220593,
genotype with allele C of rs17821090,
genotype with allele G of rs4794701,
genotype with allele C of rs4794702,
genotype carrying allele T of rs8064252,
genotype carrying allele T of rs17220607,
genotype carrying allele G of rs8081915,
genotype with allele G of rs4794703,
genotype carrying allele T of rs4452017,
genotype carrying allele A of rs4284702,
genotype carrying allele A of rs8067946,
genotype carrying allele G of rs34773938,
genotype carrying allele G of rs17220621,
genotype possessing allele G of rs35479111,
genotype carrying allele C of rs62060346,
genotype carrying allele T of rs62060347,
genotype carrying allele G of rs62060348,
genotype with allele C of rs17833789,
genotype possessing allele G of rs9907841
genotype carrying allele T of rs62060349,
genotype carrying allele T of rs11079281,
genotype carrying allele G of rs17821126,
genotype possessing allele C of rs80243896, or
The method according to claim 2, comprising the step of determining that a subject having any one or more genotypes possessing allele A of rs59704173 is prone to buckwheat.

A method for determining the likelihood of becoming a test subject's buckwheat including a step of detecting a genotype in a DNA-containing sample derived from a subject, wherein the insertion polymorphism, deletion polymorphism, or base repeat polymorphism to be detected The type is rs140364236, rs77002482, rs5872148, rs143978112, rs67920508, rs11413212, rs67892375, rs5788185, rs36103789, rs35271333, rs34828951, rs10647236, rs148896299, rs11436341, rs5821164, rs112409672, rs111581498, rs145273475, rs2622795 The method according to claim 1, wherein the method is one or more insertion polymorphisms, deletion polymorphisms, or base repeat polymorphisms.

genotype possessing the allele ATAAGG of rs140364236,
genotype possessing the allele CAA of rs77002482,
genotype carrying allele T of rs5872148,
genotype possessing allele T of rs143978112,
genotype possessing allele C of rs67920508,
genotype possessing allele AT of rs11413212,
genotype possessing allele A of rs67892375,
genotype possessing allele AT of rs5788185,
genotype possessing allele GA of rs36103789,
genotype possessing allele T of rs35271333,
genotype possessing allele A of rs34828951,
genotype carrying allele C of rs10647236,
genotype possessing the allele GTTTA of rs148896299,
genotype possessing allele A of rs11436341,
genotype possessing allelic CT of rs5821164,
genotype carrying the allele TA of rs112409672,
genotype possessing allele AC of rs111581498,
genotype possessing the allele CCCAGCACTTTAGGAGGCTGAGG of rs145273475,
genotype carrying allele C of rs530322916,
genotype carrying the allelic CAA of rs200262366, or
The method according to claim 4, comprising the step of determining that a subject having any one or more genotypes of the genotype possessing the allele AT of rs548590979 is prone to buckwheat.

The single nucleotide polymorphism according to any one of claims 1 to 5 and / or a single nucleotide polymorphism, an insertion polymorphism, a deletion polymorphism, or a nucleotide repeat polymorphism in linkage disequilibrium with the single nucleotide polymorphism. A polynucleotide for determining the likelihood of becoming a test subject's buckwheat, which can be used as a probe or primer for detecting.

A kit for determining the likelihood of becoming a test subject's freckles, comprising a probe and / or a primer comprising the polynucleotide according to claim 6.

A composition for preventing or treating buckwheat that controls the expression of PPARGC1B gene, BNC2 gene, or HSPA12A gene or suppresses the action of the protein.