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K., MacInnis, Robert J., Maishman, Tom, Makalic, Enes, Malone, Kathleen E., Kostovska, Ivana Maleva, Mannermaa, Arto, Manoukian, Siranoush, Manson, Joann E., Margolin, Sara, Mariapun, Shivaani, Martinez, Maria Elena, Matsuo, Keitaro ORCID: 0000-0003-1761-6314, Mavroudis, Dimitrios, McKay, James, McLean, Catriona, Meijers-Heijboer, Hanne, Meindl, Alfons, Menendez, Primitiva, Menon, Usha ORCID: 0000-0003-3708-1732, Meyer, Jeffery, Miao, Hui, Miller, Nicola, Taib, Nur Aishah Mohd ORCID: 0000-0001-8419-0478, Muir, Kenneth, Mulligan, Anna Marie ORCID: 0000-0002-7239-5297, Mulot, Claire, Neuhausen, Susan L., Nevanlinna, Heli, Neven, Patrick, Nielsen, Sune F., Noh, Dong-Young, Nordestgaard, Borge G., Norman, Aaron, Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Hakan ORCID: 0000-0002-8794-9635, Olswold, Curtis, Orr, Nick, Pankratz, V. Shane, Park, Sue K., Park-Simon, Tjoung-Won, Lloyd, Rachel, Perez, Jose I. 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T., Saloustros, Emmanouil ORCID: 0000-0002-0485-0120, Sandler, Dale P., Sangrajrang, Suleeporn, Sawyer, Elinor J., Schmidt, Daniel F., Schmutzler, Rita K., Schneeweiss, Andreas, Schoemaker, Minouk J., Schumacher, Fredrick ORCID: 0000-0002-3073-7463, Schuermann, Peter, Scott, Rodney J., Scott, Christopher, Seal, Sheila, Seynaeve, Caroline, Shah, Mitul, Sharma, Priyanka ORCID: 0000-0001-8592-2239, Shen, Chen-Yang, Sheng, Grace, Sherman, Mark E., Shrubsole, Martha J., Shu, Xiao-Ou, Smeets, Ann, Sohn, Christof, Southey, Melissa C., Spinelli, John J. ORCID: 0000-0002-9119-3287, Stegmaier, Christa, Stewart-Brown, Sarah, Stone, Jennifer ORCID: 0000-0001-5077-0124, Stram, Daniel O., Surowy, Harald ORCID: 0000-0002-3595-9188, Swerdlow, Anthony ORCID: 0000-0001-5550-4159, Tamimi, Rulla, Taylor, Jack A., Tengstrom, Maria, Teo, Soo H., Terry, Mary Beth, Tessier, Daniel C., Thanasitthichai, Somchai, Thoene, Kathrin, Tollenaar, Rob A. E. 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Full text not available from this repository.

Abstract

Breast 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(1). We identified 65 new loci that are associated with overall breast cancer risk at P < 5 x 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Michailidou, KyriakiUNSPECIFIEDorcid.org/0000-0001-7065-1237UNSPECIFIED
Lindstrom, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dennis, JoeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beesley, JonathanUNSPECIFIEDorcid.org/0000-0003-1942-325XUNSPECIFIED
Hui, ShirleyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kar, SiddharthaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lemacon, AudreyUNSPECIFIEDorcid.org/0000-0002-1817-7029UNSPECIFIED
Soucy, PennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glubb, DylanUNSPECIFIEDorcid.org/0000-0002-2184-7708UNSPECIFIED
Rostamianfar, AshaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolla, Manjeet K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, QinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tyrer, JonathanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dicks, EdUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, AndrewUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, ZhaomingUNSPECIFIEDorcid.org/0000-0001-7556-3869UNSPECIFIED
Allen, JamieUNSPECIFIEDorcid.org/0000-0002-8677-2225UNSPECIFIED
Keeman, RenskeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eilber, UrsulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
French, Juliet D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chen, Xiao QingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fachal, LauraUNSPECIFIEDorcid.org/0000-0002-7256-9752UNSPECIFIED
McCue, KarenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McCart, Amy E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reed, Amy E. McCartUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ghoussaini, MayaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carroll, Jason S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jiang, XiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Finucane, HilaryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adams, MarciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adank, Muriel A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ahsan, HabibulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aittomaki, KristiinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anton-Culver, HodaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antonenkova, Natalia N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arndt, VolkerUNSPECIFIEDorcid.org/0000-0001-9320-8684UNSPECIFIED
Aronson, Kristan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arun, BanuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Auer, Paul L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bacot, FrancoisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barrdahl, MyrtoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baynes, CarolineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beckmann, Matthias W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Behrens, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benitez, JavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bermisheva, MarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bernstein, LeslieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blomqvist, CarlUNSPECIFIEDorcid.org/0000-0003-3041-1938UNSPECIFIED
Bogdanova, Natalia V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bojesen, Stig E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bonanni, BernardoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borresen-Dale, Anne-LiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brand, Judith S.UNSPECIFIEDorcid.org/0000-0002-3720-1274UNSPECIFIED
Brauch, HiltrudUNSPECIFIEDorcid.org/0000-0001-7531-2736UNSPECIFIED
Brennan, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brenner, HermannUNSPECIFIEDorcid.org/0000-0002-6129-1572UNSPECIFIED
Brinton, LouiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Broberg, PerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Broeks, AnnegienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brooks-Wilson, AngelaUNSPECIFIEDorcid.org/0000-0003-1009-6408UNSPECIFIED
Brucker, Sara Y.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Burwinkel, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Butterbach, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cai, QiuyinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cai, HuiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caldes, TrinidadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Canzian, FedericoUNSPECIFIEDorcid.org/0000-0002-4261-4583UNSPECIFIED
Carracedo, AngelUNSPECIFIEDorcid.org/0000-0003-1085-8986UNSPECIFIED
Carter, Brian D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Castelao, Jose E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chan, Tsun L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cheng, Ting-Yuan DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chia, Kee SengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Choi, Ji-YeobUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Christiansen, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clarke, Christine L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Collee, MargrietUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Conroy, Don M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cordina-Duverger, EmilieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cornelissen, StenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Cross, Simon S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Gonzalez-Neira, AnnaUNSPECIFIEDorcid.org/0000-0002-5421-2020UNSPECIFIED
Alnaes, Grethe I. GrenakerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Pinchev, MilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Plaseska-Karanfilska, DijanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prentice, RossUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Shu, Xiao-OuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smeets, AnnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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Tessier, Daniel C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thanasitthichai, SomchaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thoene, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tollenaar, Rob A. E. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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van den Ouweland, Ans M. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van der Kolk, LizetUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van der Luijt, Rob B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vincent, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vollenweider, JasonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waisfisz, QuintenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang-Gohrke, ShanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weinberg, Clarice R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wendt, CamillaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Whittemore, Alice S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wildiers, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Willett, WalterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winqvist, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolk, AlicjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, Anna H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xia, LucyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yamaji, TaikiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, Xiaohong R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yip, Cheng HarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yoo, Keun-YoungUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yu, Jyh-CherngUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zheng, WeiUNSPECIFIEDorcid.org/0000-0003-1226-070XUNSPECIFIED
Zheng, YingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhu, BinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ziogas, ArgyriosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ziv, EladUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lakhani, Sunil R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Antoniou, Antonis C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Droit, ArnaudUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andrulis, Irene L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Amos, Christopher I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Couch, Fergus J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pharoah, Paul D. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chang-Claude, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hall, PerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hunter, David J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Milne, Roger L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Closas, MontserratUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, Marjanka K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chanock, Stephen J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dunning, Alison M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Edwards, Stacey L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bader, Gary D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chenevix-Trench, GeorgiaUNSPECIFIEDorcid.org/0000-0002-1878-2587UNSPECIFIED
Simard, JacquesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kraft, PeterUNSPECIFIEDorcid.org/0000-0002-4472-8103UNSPECIFIED
Easton, Douglas F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-211589
DOI: 10.1038/nature24284
Journal or Publication Title: Nature
Volume: 551
Number: 7678
Page Range: S. 92 - 116
Date: 2017
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-4687
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; COMPREHENSIVE MOLECULAR PORTRAITS; SUSCEPTIBILITY LOCI; PATHWAY ANALYSIS; PROTEIN; EXPRESSION; MUTATIONS; ARCHITECTURE; ANNOTATION; ENHANCERSMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21158

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