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.
journal_name
Genet Epidemioljournal_title
Genetic epidemiologyauthors
Feng H,Gusev A,Pasaniuc B,Wu L,Long J,Abu-Full Z,Aittomäki K,Andrulis IL,Anton-Culver H,Antoniou AC,Arason A,Arndt V,Aronson KJ,Arun BK,Asseryanis E,Auer PL,Azzollini J,Balmaña J,Barkardottir RB,Barnes DR,Barrowdadoi
10.1002/gepi.22288subject
Has Abstractpub_date
2020-07-01 00:00:00pages
442-468issue
5eissn
0741-0395issn
1098-2272journal_volume
44pub_type
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