학술논문
Transcriptome‐wide association study of breast cancer risk by estrogen‐receptor status
Document Type
article
Author
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 BM; Clarke, Christine L; Collaborators, GEMO Study; Collaborators, EMBRACE; Collaborators, GC‐HBOC study; 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
Source
Genetic Epidemiology. 44(5)
Subject
Language
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.