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dc.contributor.authorMichailidou, Ken
dc.contributor.authorLindström, Sen
dc.contributor.authorDennis, Joeen
dc.contributor.authorBeesley, Jen
dc.contributor.authorHui, Sen
dc.contributor.authorKar, Sen
dc.contributor.authorLemaçon, Aen
dc.contributor.authorSoucy, Pen
dc.contributor.authorGlubb, Den
dc.contributor.authorRostamianfar, Aen
dc.contributor.authorBolla, MKen
dc.contributor.authorWang, Jeanen
dc.contributor.authorTyrer, Jonathanen
dc.contributor.authorDicks, Een
dc.contributor.authorLee, Andrewen
dc.contributor.authorWang, Zen
dc.contributor.authorAllen, Jamieen
dc.contributor.authorKeeman, Ren
dc.contributor.authorEilber, Uen
dc.contributor.authorFrench, JDen
dc.contributor.authorQing Chen, Xen
dc.contributor.authorFachal Vilar, Lauraen
dc.contributor.authorMcCue, Ken
dc.contributor.authorMcCart Reed, AEen
dc.contributor.authorGhoussaini, Men
dc.contributor.authorCarroll, Jasonen
dc.contributor.authorJiang, Xen
dc.contributor.authorFinucane, Hen
dc.contributor.authorAdams, Men
dc.contributor.authorAdank, MAen
dc.contributor.authorAhsan, Hen
dc.contributor.authorAittomäki, Ken
dc.contributor.authorAnton-Culver, Hen
dc.contributor.authorAntonenkova, NNen
dc.contributor.authorArndt, Ven
dc.contributor.authorAronson, KJen
dc.contributor.authorArun, Ben
dc.contributor.authorAuer, PLen
dc.contributor.authorBacot, Fen
dc.contributor.authorBarrdahl, Men
dc.contributor.authorBaynes, Cen
dc.contributor.authorBeckmann, MWen
dc.contributor.authorBehrens, Sen
dc.contributor.authorBenitez, Jen
dc.contributor.authorBermisheva, Men
dc.contributor.authorBernstein, Len
dc.contributor.authorBlomqvist, Cen
dc.contributor.authorBogdanova, NVen
dc.contributor.authorBojesen, SEen
dc.contributor.authorBonanni, Ben
dc.contributor.authorBørresen-Dale, A-Len
dc.contributor.authorBrand, JSen
dc.contributor.authorBrauch, Hen
dc.contributor.authorBrennan, Pen
dc.contributor.authorBrenner, Hen
dc.contributor.authorBrinton, Len
dc.contributor.authorBroberg, Pen
dc.contributor.authorBrock, IWen
dc.contributor.authorBroeks, Aen
dc.contributor.authorBrooks-Wilson, Aen
dc.contributor.authorBrucker, SYen
dc.contributor.authorBrüning, Ten
dc.contributor.authorBurwinkel, Ben
dc.contributor.authorButterbach, Ken
dc.contributor.authorCai, Qen
dc.contributor.authorCai, Hen
dc.contributor.authorCaldés, Ten
dc.contributor.authorCanzian, Fen
dc.contributor.authorCarracedo, Aen
dc.contributor.authorCarter, BDen
dc.contributor.authorCastelao, JEen
dc.contributor.authorChan, TLen
dc.contributor.authorDavid Cheng, T-Yen
dc.contributor.authorSeng Chia, Ken
dc.contributor.authorChoi, J-Yen
dc.contributor.authorChristiansen, Hen
dc.contributor.authorClarke, CLen
dc.contributor.authorNBCS Collaborators,en
dc.contributor.authorCollée, Men
dc.contributor.authorConroy, DMen
dc.contributor.authorCordina-Duverger, Een
dc.contributor.authorCornelissen, Sen
dc.contributor.authorCox, DGen
dc.contributor.authorCox, Aen
dc.contributor.authorCross, SSen
dc.contributor.authorCunningham, JMen
dc.contributor.authorCzene, Ken
dc.contributor.authorDaly, MBen
dc.contributor.authorDevilee, Pen
dc.contributor.authorDoheny, KFen
dc.contributor.authorDörk, Ten
dc.contributor.authorDos-Santos-Silva, Ien
dc.contributor.authorDumont, Men
dc.contributor.authorDurcan, Len
dc.contributor.authorDwek, Men
dc.contributor.authorEccles, DMen
dc.contributor.authorEkici, ABen
dc.contributor.authorEliassen, AHen
dc.contributor.authorEllberg, Cen
dc.contributor.authorElvira, Men
dc.contributor.authorEngel, Cen
dc.contributor.authorEriksson, Men
dc.contributor.authorFasching, PAen
dc.contributor.authorFigueroa, Jen
dc.contributor.authorFlesch-Janys, Den
dc.contributor.authorFletcher, Oen
dc.contributor.authorFlyger, Hen
dc.contributor.authorFritschi, Len
dc.contributor.authorGaborieau, Ven
dc.contributor.authorGabrielson, Men
dc.contributor.authorGago-Dominguez, Men
dc.contributor.authorGao, Y-Ten
dc.contributor.authorGapstur, SMen
dc.contributor.authorGarcía-Sáenz, JAen
dc.contributor.authorGaudet, MMen
dc.contributor.authorGeorgoulias, Ven
dc.contributor.authorGiles, GGen
dc.contributor.authorGlendon, Gen
dc.contributor.authorGoldberg, MSen
dc.contributor.authorGoldgar, DEen
dc.contributor.authorGonzález-Neira, Aen
dc.contributor.authorGrenaker Alnæs, GIen
dc.contributor.authorGrip, Men
dc.contributor.authorGronwald, Jen
dc.contributor.authorGrundy, Aen
dc.contributor.authorGuénel, Pen
dc.contributor.authorHaeberle, Len
dc.contributor.authorHahnen, Een
dc.contributor.authorHaiman, CAen
dc.contributor.authorHåkansson, Nen
dc.contributor.authorHamann, Uen
dc.contributor.authorHamel, Nen
dc.contributor.authorHankinson, Sen
dc.contributor.authorHarrington, Pen
dc.contributor.authorHart, SNen
dc.contributor.authorHartikainen, JMen
dc.contributor.authorHartman, Men
dc.contributor.authorHein, Aen
dc.contributor.authorHeyworth, Jen
dc.contributor.authorHicks, Ben
dc.contributor.authorHillemanns, Pen
dc.contributor.authorHo, DNen
dc.contributor.authorHollestelle, Aen
dc.contributor.authorHooning, MJen
dc.contributor.authorHoover, RNen
dc.contributor.authorHopper, JLen
dc.contributor.authorHou, M-Fen
dc.contributor.authorHsiung, C-Nen
dc.contributor.authorHuang, Gen
dc.contributor.authorHumphreys, Ken
dc.contributor.authorIshiguro, Jen
dc.contributor.authorIto, Hen
dc.contributor.authorIwasaki, Men
dc.contributor.authorIwata, Hen
dc.contributor.authorJakubowska, Aen
dc.contributor.authorJanni, Wen
dc.contributor.authorJohn, EMen
dc.contributor.authorJohnson, Nen
dc.contributor.authorJones, Ken
dc.contributor.authorJones, Men
dc.contributor.authorJukkola-Vuorinen, Aen
dc.contributor.authorKaaks, Ren
dc.contributor.authorKabisch, Men
dc.contributor.authorKaczmarek, Ken
dc.contributor.authorKang, Den
dc.contributor.authorKasuga, Yen
dc.contributor.authorKerin, MJen
dc.contributor.authorKhan, Sen
dc.contributor.authorKhusnutdinova, Een
dc.contributor.authorKiiski, JIen
dc.contributor.authorKim, S-Wen
dc.contributor.authorKnight, JAen
dc.contributor.authorKosma, V-Men
dc.contributor.authorKristensen, VNen
dc.contributor.authorKrüger, Uen
dc.contributor.authorKwong, Aen
dc.contributor.authorLambrechts, Den
dc.contributor.authorLe Marchand, Len
dc.contributor.authorLee, Een
dc.contributor.authorLee, MHen
dc.contributor.authorLee, JWen
dc.contributor.authorNeng Lee, Cen
dc.contributor.authorLejbkowicz, Fen
dc.contributor.authorLi, Jen
dc.contributor.authorLilyquist, Jen
dc.contributor.authorLindblom, Aen
dc.contributor.authorLissowska, Jen
dc.contributor.authorLo, W-Yen
dc.contributor.authorLoibl, Sen
dc.contributor.authorLong, Jen
dc.contributor.authorLophatananon, Aen
dc.contributor.authorLubinski, Jen
dc.contributor.authorLuccarini, Cen
dc.contributor.authorLux, MPen
dc.contributor.authorMa, ESKen
dc.contributor.authorMacInnis, RJen
dc.contributor.authorMaishman, Ten
dc.contributor.authorMakalic, Een
dc.contributor.authorMalone, KEen
dc.contributor.authorKostovska, IMen
dc.contributor.authorMannermaa, Aen
dc.contributor.authorManoukian, Sen
dc.contributor.authorManson, JEen
dc.contributor.authorMargolin, Sen
dc.contributor.authorMariapun, Sen
dc.contributor.authorMartinez, MEen
dc.contributor.authorMatsuo, Ken
dc.contributor.authorMavroudis, Den
dc.contributor.authorMcKay, Jen
dc.contributor.authorMcLean, Cen
dc.contributor.authorMeijers-Heijboer, Hen
dc.contributor.authorMeindl, Aen
dc.contributor.authorMenéndez, Pen
dc.contributor.authorMenon, Uen
dc.contributor.authorMeyer, Jen
dc.contributor.authorMiao, Hen
dc.contributor.authorMiller, Nen
dc.contributor.authorTaib, NAMen
dc.contributor.authorMuir, Ken
dc.contributor.authorMulligan, AMen
dc.contributor.authorMulot, Cen
dc.contributor.authorNeuhausen, SLen
dc.contributor.authorNevanlinna, Hen
dc.contributor.authorNeven, Pen
dc.contributor.authorNielsen, SFen
dc.contributor.authorNoh, D-Yen
dc.contributor.authorNordestgaard, BGen
dc.contributor.authorNorman, Aen
dc.contributor.authorOlopade, OIen
dc.contributor.authorOlson, JEen
dc.contributor.authorOlsson, Hen
dc.contributor.authorOlswold, Cen
dc.contributor.authorOrr, Nen
dc.contributor.authorPankratz, VSen
dc.contributor.authorPark, SKen
dc.contributor.authorPark-Simon, T-Wen
dc.contributor.authorLloyd, Ren
dc.contributor.authorPerez, JIAen
dc.contributor.authorPeterlongo, Pen
dc.contributor.authorPeto, Jen
dc.contributor.authorPhillips, K-Aen
dc.contributor.authorPinchev, Men
dc.contributor.authorPlaseska-Karanfilska, Den
dc.contributor.authorPrentice, Ren
dc.contributor.authorPresneau, Nen
dc.contributor.authorProkofyeva, Den
dc.contributor.authorPugh, Een
dc.contributor.authorPylkäs, Ken
dc.contributor.authorRack, Ben
dc.contributor.authorRadice, Pen
dc.contributor.authorRahman, Nen
dc.contributor.authorRennert, Gen
dc.contributor.authorRennert, HSen
dc.contributor.authorRhenius, Valerieen
dc.contributor.authorRomero, Aen
dc.contributor.authorRomm, Jen
dc.contributor.authorRuddy, KJen
dc.contributor.authorRüdiger, Ten
dc.contributor.authorRudolph, Aen
dc.contributor.authorRuebner, Men
dc.contributor.authorRutgers, EJTen
dc.contributor.authorSaloustros, Een
dc.contributor.authorSandler, DPen
dc.contributor.authorSangrajrang, Sen
dc.contributor.authorSawyer, EJen
dc.contributor.authorSchmidt, DFen
dc.contributor.authorSchmutzler, RKen
dc.contributor.authorSchneeweiss, Aen
dc.contributor.authorSchoemaker, MJen
dc.contributor.authorSchumacher, Fen
dc.contributor.authorSchürmann, Pen
dc.contributor.authorScott, RJen
dc.contributor.authorScott, Cen
dc.contributor.authorSeal, Sen
dc.contributor.authorSeynaeve, Cen
dc.contributor.authorShah, Mitulen
dc.contributor.authorSharma, Pen
dc.contributor.authorShen, C-Yen
dc.contributor.authorSheng, Gen
dc.contributor.authorSherman, MEen
dc.contributor.authorShrubsole, MJen
dc.contributor.authorShu, X-Oen
dc.contributor.authorSmeets, Aen
dc.contributor.authorSohn, Cen
dc.contributor.authorSouthey, MCen
dc.contributor.authorSpinelli, JJen
dc.contributor.authorStegmaier, Cen
dc.contributor.authorStewart-Brown, Sen
dc.contributor.authorStone, Jen
dc.contributor.authorStram, DOen
dc.contributor.authorSurowy, Hen
dc.contributor.authorSwerdlow, Aen
dc.contributor.authorTamimi, Ren
dc.contributor.authorTaylor, JAen
dc.contributor.authorTengström, Men
dc.contributor.authorTeo, SHen
dc.contributor.authorBeth Terry, Men
dc.contributor.authorTessier, DCen
dc.contributor.authorThanasitthichai, Sen
dc.contributor.authorThöne, Ken
dc.contributor.authorTollenaar, RAEMen
dc.contributor.authorTomlinson, Ien
dc.contributor.authorTong, Len
dc.contributor.authorTorres, Den
dc.contributor.authorTruong, Ten
dc.contributor.authorTseng, C-Cen
dc.contributor.authorTsugane, Sen
dc.contributor.authorUlmer, H-Uen
dc.contributor.authorUrsin, Gen
dc.contributor.authorUntch, Men
dc.contributor.authorVachon, Cen
dc.contributor.authorvan Asperen, CJen
dc.contributor.authorVan Den Berg, Den
dc.contributor.authorvan den Ouweland, AMWen
dc.contributor.authorvan der Kolk, Len
dc.contributor.authorvan der Luijt, RBen
dc.contributor.authorVincent, Den
dc.contributor.authorVollenweider, Jen
dc.contributor.authorWaisfisz, Qen
dc.contributor.authorWang-Gohrke, Sen
dc.contributor.authorWeinberg, CRen
dc.contributor.authorWendt, Cen
dc.contributor.authorWhittemore, ASen
dc.contributor.authorWildiers, Hen
dc.contributor.authorWillett, Wen
dc.contributor.authorWinqvist, Ren
dc.contributor.authorWolk, Aen
dc.contributor.authorWu, AHen
dc.contributor.authorXia, Len
dc.contributor.authorYamaji, Ten
dc.contributor.authorYang, XRen
dc.contributor.authorHar Yip, Cen
dc.contributor.authorYoo, K-Yen
dc.contributor.authorYu, J-Cen
dc.contributor.authorZheng, Wen
dc.contributor.authorZheng, Yen
dc.contributor.authorZhu, Ben
dc.contributor.authorZiogas, Aen
dc.contributor.authorZiv, Een
dc.contributor.authorABCTB Investigators,en
dc.contributor.authorConFab/AOCS Investigators,en
dc.contributor.authorLakhani, SRen
dc.contributor.authorAntoniou, Antonisen
dc.contributor.authorDroit, Aen
dc.contributor.authorAndrulis, ILen
dc.contributor.authorAmos, CIen
dc.contributor.authorCouch, FJen
dc.contributor.authorPharoah, Paulen
dc.contributor.authorChang-Claude, Jen
dc.contributor.authorHall, Pen
dc.contributor.authorHunter, DJen
dc.contributor.authorMilne, RLen
dc.contributor.authorGarcía-Closas, Men
dc.contributor.authorSchmidt, MKen
dc.contributor.authorChanock, SJen
dc.contributor.authorDunning, Alisonen
dc.contributor.authorEdwards, SLen
dc.contributor.authorBader, GDen
dc.contributor.authorChenevix-Trench, Gen
dc.contributor.authorSimard, Jen
dc.contributor.authorKraft, Pen
dc.contributor.authorEaston, Douglasen
dc.date.accessioned2017-11-07T16:48:59Z
dc.date.available2017-11-07T16:48:59Z
dc.date.issued2017-10-23en
dc.identifier.issn0028-0836
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/268158
dc.description.abstractBreast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.
dc.description.sponsorshipWe thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project, funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie, de la Science et de l’Innovation du Québec’ through Genome Québec, and the Quebec Breast Cancer Foundation; the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH Grants U19 CA148065 and X01HG007492); and Cancer Research UK (C1287/A10118 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec, grant PSR-SIIRI-701. Combining of the GWAS data was supported in part by The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE, part of the GAME-ON initiative).
dc.languageengen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.subjectNBCS Collaboratorsen
dc.subjectABCTB Investigatorsen
dc.subjectConFab/AOCS Investigatorsen
dc.titleAssociation analysis identifies 65 new breast cancer risk locien
dc.typeArticle
prism.publicationDate2017en
prism.publicationNameNatureen
dc.identifier.doi10.17863/CAM.14358
dcterms.dateAccepted2017-09-17en
rioxxterms.versionofrecord10.1038/nature24284en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-10-23en
dc.contributor.orcidDennis, Joe [0000-0003-4591-1214]
dc.contributor.orcidWang, Jean [0000-0002-9139-0627]
dc.contributor.orcidTyrer, Jonathan [0000-0003-3724-4757]
dc.contributor.orcidLee, Andrew [0000-0003-0677-0252]
dc.contributor.orcidAllen, Jamie [0000-0002-8677-2225]
dc.contributor.orcidFachal Vilar, Laura [0000-0002-7256-9752]
dc.contributor.orcidCarroll, Jason [0000-0003-3643-0080]
dc.contributor.orcidRhenius, Valerie [0000-0003-4215-3235]
dc.contributor.orcidAntoniou, Antonis [0000-0001-9223-3116]
dc.contributor.orcidPharoah, Paul [0000-0001-8494-732X]
dc.contributor.orcidDunning, Alison [0000-0001-6651-7166]
dc.contributor.orcidEaston, Douglas [0000-0003-2444-3247]
dc.identifier.eissn1476-4687
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (16561)
pubs.funder-project-idCancer Research UK (20861)
pubs.funder-project-idCancer Research UK (10124)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (656144)
pubs.funder-project-idNational Cancer Institute (NCI) (U19CA148065)
pubs.funder-project-idNational Cancer Institute (NCI) (R01CA128978)
pubs.funder-project-idCancer Research UK (C14303_do not transfer)
pubs.funder-project-idEC FP7 CP (223175)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (634935)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (633784)
pubs.funder-project-idCancer Research UK (CRUK-A10710)
pubs.funder-project-idCancer Research UK (CRUK-A16563)
pubs.funder-project-idCancer Research UK (CRUK-A10118)
cam.issuedOnline2017-10-23en
rioxxterms.freetoread.startdate2018-04-23


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