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Feng, Helian; Gusev, Alexander; Pasaniuc, Bogdan; Wu, Lang; Long, Jirong; Abu-full, Zomoroda; Aittomaki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Antoniou, Antonis C.; Arason, Adalgeir; Arndt, Volker; Aronson, Kristan J.; Arun, Banu K.; Asseryanis, Ella; Auer, Paul L.; Azzollini, Jacopo; Balmana, Judith; Barkardottir, Rosa B.; Barnes, Daniel R.; Barrowdale, Daniel; Beckmann, Matthias W.; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bialkowska, Katarzyna; Blanco, Ana; Blomqvist, Carl; Boeckx, Bram; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Borg, Ake; Brauch, Hiltrud; Brenner, Hermann; Briceno, Ignacio; Broeks, Annegien; Bruening, Thomas; Burwinkel, Barbara; Cai, Qiuyin; Caldes, Trinidad; Caligo, Maria A.; Campbell, Ian; Canisius, Sander; Campa, Daniele; Carter, Brian D.; Carter, Jonathan; Castelao, Jose E.; Chang-Claude, Jenny; Chanock, Stephen J.; Christiansen, Hans; Chung, Wendy K.; Claes, Kathleen B. M.; Clarke, Christine L.; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Cybulski, Cezary; Czene, Kamila; Daly, Mary B.; de la Hoya, Miguel; De Leeneer, Kim; Dennis, Joe; Devilee, Peter; Diez, Orland; Domchek, Susan M.; Doerk, Thilo; dos-Santos-Silva, Isabel; Dunning, Alison M.; Dwek, Miriam; Eccles, Diana M.; Ejlertsen, Bent; Ellberg, Carolina; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A.; Fletcher, Olivia; Flyger, Henrik; Fostira, Florentia; Friedman, Eitan; Fritschi, Lin; Frost, Debra; Gabrielson, Marike; Ganz, Patricia A.; Gapstur, Susan M.; Garber, Judy; Garcia-Closas, Montserrat; Garcia-Saenz, Jose A.; Gaudet, Mia M.; Giles, Graham G.; Glendon, Gord; Godwin, Andrew K.; Goldberg, Mark S.; Goldgar, David E.; Gonzalez-Neira, Anna; Greene, Mark H.; Gronwald, Jacek; Guenel, Pascal; Haiman, Christopher A.; Hall, Per; Hamann, Ute; Hake, Christopher; He, Wei; Heyworth, Jane; Hogervorst, Frans B. L.; Hollestelle, Antoinette; Hooning, Maartje J.; Hoover, Robert N.; Hopper, John L.; Huang, Guanmengqian; Hulick, Peter J.; Humphreys, Keith; Imyanitov, Evgeny N.; Isaacs, Claudine; Jakimovska, Milena; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jankowitz, Rachel C.; John, Esther M.; Johnson, Nichola; Joseph, Vijai; Jung, Audrey; Karlan, Beth Y.; Khusnutdinova, Elza; Kiiski, Johanna; Konstantopoulou, Irene; Kristensen, Vessela N.; Laitman, Yael; Lambrechts, Diether; Lazaro, Conxi; Leroux, Dominique; Leslie, Goska; Lester, Jenny; Lesueur, Fabienne; Lindor, Noralane; Lindstrom, Sara; Lo, Wing-Yee; Loud, Jennifer T.; Lubinski, Jan; Makalic, Enes; Mannermaa, Arto; Manoochehri, Mehdi; Manoukian, Siranoush; Margolin, Sara; Martens, John W. M.; Martinez, Maria E.; Matricardi, Laura; Maurer, Tabea; Mavroudis, Dimitrios; McGuffog, Lesley; Meindl, Alfons; Menon, Usha; Michailidou, Kyriaki; Kapoor, Pooja M.; Miller, Austin; Montagna, Marco; Moreno, Fernando; Moserle, Lidia; Mulligan, Anna M.; Muranen, Taru A.; Nathanson, Katherine L.; Neuhausen, Susan L.; Nevanlinna, Heli; Nevelsteen, Ines; Nielsen, Finn C.; Nikitina-Zake, Liene; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo; Olsson, Hakan; Osorio, Ana; Papp, Janos; Park-Simon, Tjoung-Won; Parsons, Michael T.; Pedersen, Inge S.; Peixoto, Ana; Peterlongo, Paolo; Peto, Julian; Pharoah, Paul D. P.; Phillips, Kelly-Anne; Plaseska-Karanfilska, Dijana; Poppe, Bruce; Pradhan, Nisha; Prajzendanc, Karolina; Presneau, Nadege; Punie, Kevin; Pylkas, Katri; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad Usman; Rennert, Gad; Risch, Harvey A.; Robson, Mark; Romero, Atocha; Saloustros, Emmanouil; Sandler, Dale P.; Santos, Catarina; Sawyer, Elinor J.; Schmidt, Marjanka K.; Schmidt, Daniel F.; Schmutzler, Rita K.; Schoemaker, Minouk J.; Scott, Rodney J.; Sharma, Priyanka; Shu, Xiao-Ou; Simard, Jacques; Singer, Christian F.; Skytte, Anne-Bine; Soucy, Penny; Southey, Melissa C.; Spinelli, John J.; Spurdle, Amanda B.; Stone, Jennifer; Swerdlow, Anthony J.; Tapper, William J.; Taylor, Jack A.; Teixeira, Manuel R.; Terry, Mary Beth; Teule, Alex; Thomassen, Mads; Thoene, Kathrin; Thull, Darcy L.; Tischkowitz, Marc; Toland, Amanda E.; Tollenaar, Rob A. E. M.; Torres, Diana; Truong, Therese; Tung, Nadine; Vachon, Celine M.; Asperen, Christi J. van; Ouweland, Ans M. W. van den; Rensburg, Elizabeth J. van; Vega, Ana; Viel, Alessandra; Vieiro-Balo, Paula; Wang, Qin; Wappenschmidt, Barbara; Weinberg, Clarice R.; Weitzel, Jeffrey N.; Wendt, Camilla; Winqvist, Robert; Yang, Xiaohong R.; Yannoukakos, Drakoulis; Ziogas, Argyrios; Milne, Roger L.; Easton, Douglas F.; Chenevix-Trench, Georgia; Zheng, Wei; Kraft, Peter und Jiang, Xia (2020): Transcriptome-wide association study of breast cancer risk by estrogen-receptor status. In: Genetic Epidemiology, Bd. 44, Nr. 5: S. 442-468

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Abstract

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.

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