Loci associated with skin pigmentation identified in African populations

Abstract

Despite the wide range of skin pigmentation in humans, little is known about its genetic basis in global populations. Examining ethnically diverse African genomes, we identify variants in or near <i>SLC24A5</i>, <i>MFSD12</i>, <i>DDB1</i>, <i>TMEM138</i>, <i>OCA2</i>, and <i>HERC2</i> that are significantly associated with skin pigmentation. Genetic evidence indicates that the light pigmentation variant at <i>SLC24A5</i> was introduced into East Africa by gene flow from non-Africans. At all other loci, variants associated with dark pigmentation in Africans are identical by descent in South Asian and Australo-Melanesian populations. Functional analyses indicate that <i>MFSD12</i> encodes a lysosomal protein that affects melanogenesis in zebrafish and mice, and that mutations in melanocyte-specific regulatory regions near <i>DDB1/TMEM138</i> correlate with expression of ultraviolet response genes under selection in Eurasians.