Genome-wide association study of Asian women identifies putative mammographic density-associated loci

Background Mammographic density (MD) is a strong, heritable risk factor for breast cancer. To date, 55 independent MD-associated genetic loci have been identified through genome-wide association studies (GWASs) in women of European ancestry; however, no studies have been reported in Asian women. Methods To identify novel loci, we conducted genome-wide association studies (GWASs) of absolute dense, absolute nondense, and percentage area and volumetric densities, adjusting for age, body mass index (BMI), and ancestry-informative principal components, in a multi-ethnic cohort of 2,951 Asian women attending opportunistic mammography screening. We selected 175 novel loci that were associated with at least one MD phenotype at P < 5 × 10 − 6 for (a) replication in an independent set of 401 Asian breast cancer cases, using density measurements from the unaffected breasts, (b) evaluation in a GWAS meta-analysis of MD in 27,900 women of European ancestry and (c) evaluation with breast cancer risk in Asian women. Results Four of the 175 loci were replicated in women of Asian ancestry at P < 0.05, with directions of association that were consistent with those observed in the GWAS. The rs7018644 SNP at the 9p13.1 locus was the only loci replicated in both Asian and European cohorts. In addition, eight SNPs were also associated with breast cancer risk ( P < 0.05) in a GWAS meta-analysis of Asian women. Conclusion This study identifies potential novel MD-associated loci in Asian women. Replication in a larger Asian study is needed to confirm these findings.