@article{8670799,
  abstract     = {{Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype(1-3). To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 x 10(-8)), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.}},
  author       = {{Zhang, Haoyu and Ahearn, Thomas U. and Lecarpentier, Julie and Barnes, Daniel and Beesley, Jonathan and Qi, Guanghao and Jiang, Xia and O’Mara, Tracy A. and Zhao, Ni and Bolla, Manjeet K. and Dunning, Alison M. and Dennis, Joe and Wang, Qin and Ful, Zumuruda Abu and Aittomäki, Kristiina and Andrulis, Irene L. and Anton-Culver, Hoda and Arndt, Volker and Aronson, Kristan J. and Arun, Banu K. and Auer, Paul L. and Azzollini, Jacopo and Barrowdale, Daniel and Becher, Heiko and Beckmann, Matthias W. and Behrens, Sabine and Benitez, Javier and Bermisheva, Marina and Bialkowska, Katarzyna and Blanco, Ana and Blomqvist, Carl and Bogdanova, Natalia V. and Bojesen, Stig E. and Bonanni, Bernardo and Bondavalli, Davide and Borg, Ake and Brauch, Hiltrud and Brenner, Hermann and Briceno, Ignacio and Broeks, Annegien and Brucker, Sara Y. and Brüning, Thomas and Burwinkel, Barbara and Buys, Saundra S. and Byers, Helen and Caldés, Trinidad and Caligo, Maria A. and Calvello, Mariarosaria and Campa, Daniele and Castelao, Jose E. and Chang-Claude, Jenny and Chanock, Stephen J. and Christiaens, Melissa and Christiansen, Hans and Chung, Wendy K. and Claes, Kathleen and Clarke, Christine L. and Cornelissen, Sten and Couch, Fergus J. and Cox, Angela and Cross, Simon S. and Czene, Kamila and Daly, Mary B. and Devilee, Peter and Diez, Orland and Domchek, Susan M. and Dörk, Thilo and Dwek, Miriam and Eccles, Diana M. and Ekici, Arif B. and Evans, D. Gareth and Fasching, Peter A. and Figueroa, Jonine and Foretova, Lenka and Fostira, Florentia and Friedman, Eitan and Frost, Debra and Gago-Dominguez, Manuela and Gapstur, Susan M. and Garber, Judy and García-Sáenz, José A. and Gaudet, Mia M. and Gayther, Simon A. and Giles, Graham G. and Godwin, Andrew K. and Goldberg, Mark S. and Goldgar, David E. and González-Neira, Anna and Greene, Mark H. and Gronwald, Jacek and Guénel, Pascal and Häberle, Lothar and Hahnen, Eric and Haiman, Christopher A. and Hake, Christopher R. and Hall, Per and Hamann, Ute and Harkness, Elaine F. and Heemskerk-Gerritsen, Bernadette A. M. and Hillemanns, Peter and Hogervorst, Frans B. L. and Holleczek, Bernd and Hollestelle, Antoinette and Hooning, Maartje J. and Hoover, Robert N. and Hopper, John L. and Howell, Anthony and Huebner, Hanna and Hulick, Peter J. and Imyanitov, Evgeny N. and Isaacs, Claudine and Izatt, Louise and Jager, Agnes and Jakimovska, Milena and Jakubowska, Anna and James, Paul and Janavicius, Ramunas and Janni, Wolfgang and John, Esther M. and Jones, Michael E. and Jung, Audrey and Kaaks, Rudolf and Kapoor, Pooja Middha and Karlan, Beth Y. and Keeman, Renske and Khan, Sofia and Khusnutdinova, Elza and Kitahara, Cari M. and Ko, Yon-Dschun and Konstantopoulou, Irene and Koppert, Linetta B. and Koutros, Stella and Kristensen, Vessela N. and Laenkholm, Anne-Vibeke and Lambrechts, Diether and Larsson, Susanna C. and Laurent-Puig, Pierre and Lazaro, Conxi and Lazarova, Emilija and Lejbkowicz, Flavio and Leslie, Goska and Lesueur, Fabienne and Lindblom, Annika and Lissowska, Jolanta and Lo, Wing-Yee and Loud, Jennifer T. and Lubinski, Jan and Lukomska, Alicja and MacInnis, Robert J. and Mannermaa, Arto and Manoochehri, Mehdi and Manoukian, Siranoush and Margolin, Sara and Martinez, Maria Elena and Matricardi, Laura and McGuffog, Lesley and McLean, Catriona and Mebirouk, Noura and Meindl, Alfons and Menon, Usha and Miller, Austin and Mingazheva, Elvira and Montagna, Marco and Mulligan, Anna Marie and Mulot, Claire and Muranen, Taru A. and Nathanson, Katherine L. and Neuhausen, Susan L. and Nevanlinna, Heli and Neven, Patrick and Newman, William G. and Nielsen, Finn C. and Nikitina-Zake, Liene and Nodora, Jesse and Offit, Kenneth and Olah, Edith and Olopade, Olufunmilayo I. and Olsson, Håkan and Orr, Nick and Papi, Laura and Papp, Janos and Park-Simon, Tjoung-Won and Parsons, Michael T. and Peissel, Bernard and Peixoto, Ana and Peshkin, Beth and Peterlongo, Paolo and Peto, Julian and Phillips, Kelly-Anne and Piedmonte, Marion and Plaseska-Karanfilska, Dijana and Prajzendanc, Karolina and Prentice, Ross and Prokofyeva, Darya and Rack, Brigitte and Radice, Paolo and Ramus, Susan J. and Rantala, Johanna and Rashid, Muhammad U. and Rennert, Gad and Rennert, Hedy S. and Risch, Harvey A. and Romero, Atocha and Rookus, Matti A. and Rübner, Matthias and Rüdiger, Thomas and Saloustros, Emmanouil and Sampson, Sarah and Sandler, Dale P. and Sawyer, Elinor J. and Scheuner, Maren T. and Schmutzler, Rita K. and Schneeweiss, Andreas and Schoemaker, Minouk J. and Schöttker, Ben and Schürmann, Peter and Senter, Leigha and Sharma, Priyanka and Sherman, Mark E. and Shu, Xiao-Ou and Singer, Christian F. and Smichkoska, Snezhana and Soucy, Penny and Southey, Melissa C. and Spinelli, John J. and Stone, Jennifer and Stoppa-Lyonnet, Dominique and Swerdlow, Anthony J. and Szabo, Csilla I. and Tamimi, Rulla M. and Tapper, William J. and Taylor, Jack A. and Teixeira, Manuel R. and Terry, MaryBeth and Thomassen, Mads and Thull, Darcy L. and Tischkowitz, Marc and Toland, Amanda E. and Tollenaar, Rob A. E. M. and Tomlinson, Ian and Torres, Diana and Troester, Melissa A. and Truong, Thérèse and Tung, Nadine and Untch, Michael and Vachon, Celine M. and van den Ouweland, Ans M. W. and van der Kolk, Lizet E. and van Veen, Elke M. and vanRensburg, Elizabeth J. and Vega, Ana and Wappenschmidt, Barbara and Weinberg, Clarice R. and Weitzel, Jeffrey N. and Wildiers, Hans and Winqvist, Robert and Wolk, Alicja and Yang, Xiaohong R. and Yannoukakos, Drakoulis and Zheng, Wei and Zorn, Kristin K. and Milne, Roger L. and Kraft, Peter and Simard, Jacques and Pharoah, Paul D. P. and Michailidou, Kyriaki and Antoniou, Antonis C. and Schmidt, Marjanka K. and Chenevix-Trench, Georgia and Easton, Douglas F. and Chatterjee, Nilanjan and García-Closas, Montserrat}},
  issn         = {{1061-4036}},
  journal      = {{NATURE GENETICS}},
  keywords     = {{Genetics,MUTATION CARRIERS,RISK,HERITABILITY,METAANALYSIS,MODIFIERS,BRCA1}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{572--581}},
  title        = {{Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses}},
  url          = {{http://doi.org/10.1038/s41588-020-0609-2}},
  volume       = {{52}},
  year         = {{2020}},
}

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