An Unexpectedly Complex Architecture for Skin Pigmentation in Africans

• Published in: Cell Vol. 171; no. 6; pp. 1340 - 1353.e14
• Main Authors: Martin, Alicia R., Lin, Meng, Granka, Julie M., Myrick, Justin W., Liu, Xiaomin, Sockell, Alexandra, Atkinson, Elizabeth G., Werely, Cedric J., Möller, Marlo, Sandhu, Manjinder S., Kingsley, David M., Hoal, Eileen G., Liu, Xiao, Daly, Mark J., Feldman, Marcus W., Gignoux, Christopher R., Bustamante, Carlos D., Henn, Brenna M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.11.2017
• Subjects: Africa; Africans; Black People - genetics; genes; heritability; human evolution; Humans; latitude; loci; phenotype; pigmentation; Polymorphism, Single Nucleotide; population genetics; Skin Pigmentation; Southern Africa; surveys; variance; Africa; Southern Africa; pigmentation; population genetics; human evolution; Africa; heritability
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2017.11.015

Approximately 15 genes have been directly associated with skin pigmentation variation in humans, leading to its characterization as a relatively simple trait. However, by assembling a global survey of quantitative skin pigmentation phenotypes, we demonstrate that pigmentation is more complex than previously assumed, with genetic architecture varying by latitude. We investigate polygenicity in the KhoeSan populations indigenous to southern Africa who have considerably lighter skin than equatorial Africans. We demonstrate that skin pigmentation is highly heritable, but known pigmentation loci explain only a small fraction of the variance. Rather, baseline skin pigmentation is a complex, polygenic trait in the KhoeSan. Despite this, we identify canonical and non-canonical skin pigmentation loci, including near SLC24A5, TYRP1, SMARCA2/VLDLR, and SNX13, using a genome-wide association approach complemented by targeted resequencing. By considering diverse, under-studied African populations, we show how the architecture of skin pigmentation can vary across humans subject to different local evolutionary pressures. [Display omitted] •Skin pigmentation in Africans is far more polygenic than light skin in Eurasians•Southern African KhoeSan populations have lighter skin compared to equatorial Africans•Highly heritable KhoeSan skin color variation is poorly explained by known genes•The study of African skin color identifies novel and canonical pigmentation genes The genetic architecture of skin pigmentation is highly complex, varies across human populations, and is subject to distinct geographical evolutionary pressures.