TWAS Uncovers Additional Breast Cancer Susceptibility Genes

A study uncovering several new breast cancer susceptibility genes is presented in the American Journal of Human Genetics this week. To date, genome-wide association studies (GWAS) have identified more than 200 genomic loci for breast cancer risk, yet these genetic variants account for only a small proportion of the disease's heritability, suggesting that other variants have yet to discovered. Transcriptome-wide association studies (TWASs), meanwhile, have identified dozens of genes whose expression is significantly associated with breast cancer and its subtypes, but these genes account for only a small proportion of known GWAS loci of breast cancer. To further investigate, a group led by University of Chicago scientists performed joint TWAS analyses of breast cancer by combining TWAS information from multiple tissues. The TWAS method was then applied to summary statistics from a meta-analysis of data from 122,977 breast cancer cases and 105,974 controls in the Breast Cancer Association Consortium and 10,534 breast cancer cases and 185,116 controls in UK Biobank. Among the researchers' findings are 309 genes that are significantly associated with breast cancer, including 17 genes located in eight region not previously implicated in the disease and 292 genes located in 100 known GWAS loci. Based on the results, "future studies in diverse populations and with a focus on homogeneous phenotypes of breast cancer using innovative TWAS methodology are warranted," the authors write. "There is potential to map out most candidate genes in GWAS loci of breast cancer, the most common malignancy affecting women across the world."