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Transcriptome-wide Association Study of Breast Cancer Risk by Estrogen-Receptor Status

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Authors
Feng, Helian
Gusev, Alexander
Pasaniuc, Bogdan
Wu, Lang
Long, Jirong
Abu-Full, Zomoroda
Aittomäki, 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
Balmaña, Judith
Barkardottir, Rosa B
Barnes, Daniel R
Barrowdale, Daniel
Beckmann, Matthias W
Behrens, Sabine
Benitez, Javier
Bermisheva, Marina
Białkowska, 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
Brüning, Thomas
Burwinkel, Barbara
Cai, Qiuyin
Caldés, 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
Dörk, 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
García-Closas, Montserrat
García-Sáenz, José A
Gaudet, Mia M
Giles, Graham G
Glendon, Gord
Godwin, Andrew K
Goldberg, Mark S
Goldgar, David E
González-Neira, Anna
Greene, Mark H
Gronwald, Jacek
Guénel, 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 I
Konstantopoulou, Irene
Kristensen, Vessela N
Laitman, Yael
Lambrechts, Diether
Lazaro, Conxi
Leroux, Dominique
Leslie, Goska
Lester, Jenny
Lesueur, Fabienne
Lindor, Noralane
Lindström, Sara
Lo, Wing-Yee
Loud, Jennifer T
Lubiński, 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 I
Olsson, Håkan
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
Pylkäs, 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
Teulé, Alex
Thomassen, Mads
Thöne, Kathrin
Thull, Darcy L
Tischkowitz, Marc
Toland, Amanda E
Tollenaar, Rob A E M
Torres, Diana
Truong, Thérèse
Tung, Nadine
Vachon, Celine M
van Asperen, Christi J
van den Ouweland, Ans M W
van Rensburg, Elizabeth J
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
Jiang, Xia
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Issue Date
2020-03-01

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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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https://onlinelibrary.wiley.com/doi/full/10.1002/gepi.22288
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English Journal Articles (Peer Reviewed)

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