Abstract:
Genome-wide association studies (GWAS) have identified more than 170 breast cancer
susceptibility loci. Here we hypothesize that some risk-associated variants might act in nonbreast
tissues, specifically adipose tissue and immune cells from blood and spleen. Using
expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously
unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen
receptor (ER)-negative breast cancer, several with a known immune function. We determine
the directional effect of gene expression on disease risk measured based on single and
multiple eQTL. In addition, using a gene-based test of association that considers eQTL from
multiple tissues, we identify seven (and four) regions with variants associated with overall
(and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further
investigation of the function of the implicated genes in breast and immune cells may provide
insights into the etiology of breast cancer.
