A genome-wide association study of skin and iris pigmentation among individuals of South Asian ancestry

Abstract

SouthAsia has a complex history ofmigrations and is characterized by substantial pigmentary and genetic diversity. For this reason, it is an ideal region to study the genetic architecture of normal pigmentation variation. Here, we present a meta-analysis of two genome-wide association studies (GWASs) of skin pigmentation using skin reflectance (M-index) as a quantitative phenotype. The meta-analysis includes a sample of individuals of South Asian descent living in Canada (N48), and a sample of individuals from two caste and four tribal groups fromWestMaharashtra, India (N480).We also present the firstGWAS of iris color in SouthAsian populations. This GWAS was based on quantitativemeasures of iris color obtained fromhigh-resolution iris pictures.We identified genome-wide significant associations of variants within the well-known gene SLC24A5, including the nonsynonymous rs1426654 polymorphism,with both skin pigmentation and iris color, highlighting the pleiotropic effects of this gene on pigmentation. Variants in the HERC2 gene (e.g., rs12913832) were also associated with iris color and iris heterochromia. Our study emphasizes the usefulness of quantitativemethods to study iris color variation.We also identified novel genome-wide significant associationswith skin pigmentation and iris color, butwe could not replicate these associations due to the lack of independent samples. Itwill be critical to expand the number of studies in South Asian populations in order to better understand the genetic variation driving the diversity of skin pigmentation and iris color observed in this region.