Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

Feng, H; Gusev, A; Pasaniuc, B; Wu, L; Long, J; Abu-full, Z; Aittomaki, K; Andrulis, IL; Anton-Culver, H; Antoniou, AC; Arason, A; Arndt, V; Aronson, KJ; Arun, BK; Asseryanis, E; Auer, PL; Azzollini, J; Balmana, J; Barkardottir, RB; Barnes, DR; Barrowdale, D; Beckmann, MW; Behrens, S; Benitez, J; Bermisheva, M; Bialkowska, K; Blanco, A; Blomqvist, C; Boeckx, B; Bogdanova, NV; Bojesen, SE; Bolla, MK; Bonanni, B; Borg, A; Brauch, H; Brenner, H; Briceno, I; Broeks, A; Bruening, T; Burwinkel, B; Cai, Q; Caldes, T; Caligo, MA; Campbell, I; Canisius, S; Campa, D; Carter, BD; Carter, J; Castelao, JE; Chang-Claude, J; Chanock, SJ; Christiansen, H; Chung, WK; Claes, KBM; Clarke, CL; Couch, FJ; Cox, A; Cross, SS; Cybulski, C; Czene, K; Daly, MB; de la  Hoya, M; De Leeneer, K; Dennis, J; Devilee, P; Diez, O; Domchek, SM; Doerk, T; dos-Santos-Silva, I; Dunning, AM; Dwek, M; Eccles, DM; Ejlertsen, B; Ellberg, C; Engel, C; Eriksson, M; Fasching, PA; Fletcher, O; Flyger, H; Fostira, F; Friedman, E; Fritschi, L; Frost, D; Gabrielson, M; Ganz, PA; Gapstur, SM; Garber, J; Garcia-Closas, M; Garcia-Saenz, JA; Gaudet, MM; Giles, GG; Glendon, G; Godwin, AK; Goldberg, MS; Goldgar, DE; Gonzalez-Neira, A; Greene, MH; Gronwald, J; Guenel, P; Haiman, CA; Hall, P; Hamann, U; Hake, C; He, W; Heyworth, J; Hogervorst, FBL; Hollestelle, A; Hooning, MJ; Hoover, RN; Hopper, JL; Huang, G; Hulick, PJ; Humphreys, K; Imyanitov, EN; Isaacs, C; Jakimovska, M; Jakubowska, A; James, P; Janavicius, R; Jankowitz, RC; John, EM; Johnson, N; Joseph, V; Jung, A; Karlan, BY; Khusnutdinova, E; Kiiski, J; Konstantopoulou, I; Kristensen, VN; Laitman, Y; Lambrechts, D; Lazaro, C; Leroux, D; Leslie, G; Lester, J; Lesueur, F; Lindor, N; Lindstrom, S; Lo, W-Y; Loud, JT; Lubinski, J; Makalic, E; Mannermaa, A; Manoochehri, M; Manoukian, S; Margolin, S; Martens, JWM; Martinez, ME; Matricardi, L; Maurer, T; Mavroudis, D; McGuffog, L; Meindl, A; Menon, U; Michailidou, K; Kapoor, PM; Miller, A; Montagna, M; Moreno, F; Moserle, L; Mulligan, AM; Muranen, TA; Nathanson, KL; Neuhausen, SL; Nevanlinna, H; Nevelsteen, I; Nielsen, FC; Nikitina-Zake, L; Offit, K; Olah, E; Olopade, O; Olsson, H; Osorio, A; Papp, J; Park-Simon, T-W; Parsons, MT; Pedersen, IS; Peixoto, A; Peterlongo, P; Peto, J; Pharoah, PDP; Phillips, K-A; Plaseska-Karanfilska, D; Poppe, B; Pradhan, N; Prajzendanc, K; Presneau, N; Punie, K; Pylkas, K; Radice, P; Rantala, J; Rashid, MU; Rennert, G; Risch, HA; Robson, M; Romero, A; Saloustros, E; Sandler, DP; Santos, C; Sawyer, EJ; Schmidt, MK; Schmidt, DF; Schmutzler, RK; Schoemaker, MJ; Scott, RJ; Sharma, P; Shu, X-O; Simard, J; Singer, CF; Skytte, A-B; Soucy, P; Southey, MC; Spinelli, JJ; Spurdle, AB; Stone, J; Swerdlow, AJ; Tapper, WJ; Taylor, JA; Teixeira, MR; Terry, MB; Teule, A; Thomassen, M; Thoene, K; Thull, DL; Tischkowitz, M; Toland, AE; Tollenaar, RAEM; Torres, D; Truong, T; Tung, N; Vachon, CM; van Asperen, CJ; van den Ouweland, AMW; van Rensburg, EJ; Vega, A; Viel, A; Vieiro-Balo, P; Wang, Q; Wappenschmidt, B; Weinberg, CR; Weitzel, JN; Wendt, C; Winqvist, R; Yang, XR; Yannoukakos, D; Ziogas, A; Milne, RL; Easton, DF; Chenevix-Trench, G; Zheng, W; Kraft, P; Jiang, X

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Author

Feng, H; Gusev, A; Pasaniuc, B; Wu, L; Long, J; Abu-full, Z; Aittomaki, K; Andrulis, IL; Anton-Culver, H; Antoniou, AC; ...

Date

2020-03-01

Source Title

Genetic Epidemiology

Publisher

WILEY

University of Melbourne Author/s

Makalic, Enes; Milne, Roger; Southey, Melissa; Hopper, John; Schmidt, Daniel; James, Paul; Stone, Jennifer; Phillips, Kelly-Anne; Giles, Graham; Campbell, Ian; ...

Affiliation

Sir Peter MacCallum Department of Oncology
Melbourne School of Population and Global Health

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Document Type

Journal Article

Citations

Feng, H., Gusev, A., Pasaniuc, B., Wu, L., Long, J., Abu-full, Z., Aittomaki, K., Andrulis, I. L., Anton-Culver, H., Antoniou, A. C., Arason, A., Arndt, V., Aronson, K. J., Arun, B. K., Asseryanis, E., Auer, P. L., Azzollini, J., Balmana, J., Barkardottir, R. B. ,... Jiang, X. (2020). Transcriptome-wide association study of breast cancer risk by estrogen-receptor status. GENETIC EPIDEMIOLOGY, 44 (5), pp.442-468. https://doi.org/10.1002/gepi.22288.

Access Status

Open Access

URI

http://hdl.handle.net/11343/252347

DOI

10.1002/gepi.22288

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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