Meta-Analysis of a Multi-Ethnic, Breast Cancer Case-Control Targeted Sequencing Study

Akweley Ablorh, Harvard T.H. Chan School of Public Health, Harvard University

Breast cancer, the most commonly diagnosed cancer in American women, is a heritable disease with nearly one hundred known genetic risk factors. Using next generation sequencing, we explored the contribution of genetics at 12 GWAS-identified loci to breast cancer susceptibility in a multi-ethnic breast cancer case-control study. Methods: The study population consists of 4,611 breast cancer cases and controls (2,316 cases and 2,295 controls) from four mutually exclusive ethnicities: African, Latina, Japanese, or European American.We conducted rare variant association testing between sequenced genotypes and simulated phenotypes to compare the performance of several approaches for assessing rare variant associations across multiple ethnicities and the statistical performance of different ethnic sampling fractions, including single-ethnicity studies and studies that sample up to four...