TY - JOUR
T1 - Transcriptome-wide association study of breast cancer risk by estrogen-receptor status
AU - Feng, Helian
AU - Gusev, Alexander
AU - Pasaniuc, Bogdan
AU - Wu, Lang
AU - Long, Jirong
AU - Abu-Full, Zomoroda
AU - Aittomäki, Kristiina
AU - Andrulis, Irene L
AU - Anton-Culver, Hoda
AU - Antoniou, Antonis C
AU - Arason, Adalgeir
AU - Arndt, Volker
AU - Aronson, Kristan J
AU - Arun, Banu K
AU - Asseryanis, Ella
AU - Auer, Paul L
AU - Azzollini, Jacopo
AU - Balmaña, Judith
AU - Barkardottir, Rosa B
AU - Barnes, Daniel R
AU - Barrowdale, Daniel
AU - Beckmann, Matthias W
AU - Behrens, Sabine
AU - Benitez, Javier
AU - Bermisheva, Marina
AU - Białkowska, Katarzyna
AU - Blanco, Ana
AU - Blomqvist, Carl
AU - Boeckx, Bram
AU - Bogdanova, Natalia V
AU - Bojesen, Stig E
AU - Bolla, Manjeet K
AU - Bonanni, Bernardo
AU - Borg, Ake
AU - Brauch, Hiltrud
AU - Brenner, Hermann
AU - Briceno, Ignacio
AU - Broeks, Annegien
AU - Brüning, Thomas
AU - Burwinkel, Barbara
AU - Cai, Qiuyin
AU - Caldés, Trinidad
AU - Caligo, Maria A
AU - Campbell, Ian
AU - Canisius, Sander
AU - Campa, Daniele
AU - Carter, Brian D
AU - Carter, Jonathan
AU - Castelao, Jose E
AU - Chang-Claude, Jenny
AU - GEMO Study Collaborators
A2 - Nikitina-Zake, Liene
N1 - © 2020 The Authors. Genetic Epidemiology published by Wiley Periodicals, Inc.
PY - 2020/7
Y1 - 2020/7
N2 - 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.
AB - 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.
KW - Breast Neoplasms/genetics
KW - Estrogens/metabolism
KW - Female
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Genomics
KW - Humans
KW - Receptors, Estrogen/metabolism
KW - Risk Assessment
KW - Transcriptome
KW - Vesicular Transport Proteins/genetics
UR - http://www.scopus.com/inward/record.url?scp=85081379482&partnerID=8YFLogxK
U2 - 10.1002/gepi.22288
DO - 10.1002/gepi.22288
M3 - Article
C2 - 32115800
SN - 0741-0395
VL - 44
SP - 442
EP - 468
JO - Genetic Epidemiology
JF - Genetic Epidemiology
IS - 5
ER -