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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 SLC24A5, MFSD12, DDB1, TMEM138, OCA2, and HERC2 that are significantly associated with skin pigmentation. Genetic evidence indicates that the light pigmentation variant at SLC24A5 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 MFSD12 encodes a lysosomal protein that affects melanogenesis in zebrafish and mice, and that mutations in melanocyte-specific regulatory regions near DDB1/TMEM138 correlate with expression of ultraviolet response genes under selection in Eurasians.

SUBMITTER: Crawford NG

PROVIDER: S-EPMC5759959 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Loci associated with skin pigmentation identified in African populations.

Crawford Nicholas G NG Kelly Derek E DE Hansen Matthew E B MEB Beltrame Marcia H MH Fan Shaohua S Bowman Shanna L SL Jewett Ethan E Ranciaro Alessia A Thompson Simon S Lo Yancy Y Pfeifer Susanne P SP Jensen Jeffrey D JD Campbell Michael C MC Beggs William W Hormozdiari Farhad F Mpoloka Sununguko Wata SW Mokone Gaonyadiwe George GG Nyambo Thomas T Meskel Dawit Wolde DW Belay Gurja G Haut Jake J Rothschild Harriet H Zon Leonard L Zhou Yi Y Kovacs Michael A MA Xu Mai M Zhang Tongwu T Bishop Kevin K Sinclair Jason J Rivas Cecilia C Elliot Eugene E Choi Jiyeon J Li Shengchao A SA Hicks Belynda B Burgess Shawn S Abnet Christian C Watkins-Chow Dawn E DE Oceana Elena E Song Yun S YS Eskin Eleazar E Brown Kevin M KM Marks Michael S MS Loftus Stacie K SK Loftus Stacie K SK Pavan William J WJ Yeager Meredith M Chanock Stephen S Tishkoff Sarah A SA

Science (New York, N.Y.) 20171012 6365

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 SLC24A5, MFSD12, DDB1, TMEM138, OCA2, and HERC2 that are significantly associated with skin pigmentation. Genetic evidence indicates that the light pigmentation variant at SLC24A5 was introduced into East Africa by gene flow from non-Africans. At all othe ...[more]

PMID: 29025994

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Project description:A recent genome-wide association study (GWAS) in African descent populations identified novel loci associated with skin pigmentation. However, how genomic variations affect skin pigmentation and how these skin pigmentation gene variants affect serum 25(OH) vitamin D variation has not been explored in African Americans (AAs). In order to further understand genetic factors that affect human skin pigmentation and serum 25(OH)D variation, we performed a GWAS for skin pigmentation with 395 AAs and a replication study with 681 AAs. Then, we tested if the identified variants are associated with serum 25(OH) D concentrations in a subset of AAs (n = 591). Skin pigmentation, Melanin Index (M-Index), was measured using a narrow-band reflectometer. Multiple regression analysis was performed to identify variants associated with M-Index and to assess their role in serum 25(OH)D variation adjusting for population stratification and relevant confounding variables. A variant near the SLC24A5 gene (rs2675345) showed the strongest signal of association with M-Index (P = 4.0 x 10-30 in the pooled dataset). Variants in SLC24A5, SLC45A2 and OCA2 together account for a large proportion of skin pigmentation variance (11%). The effects of these variants on M-Index was modified by sex (P for interaction = 0.009). However, West African Ancestry (WAA) also accounts for a large proportion of M-Index variance (23%). M-Index also varies among AAs with high WAA and high Genetic Score calculated from top variants associated with M-Index, suggesting that other unknown genomic factors related to WAA are likely contributing to skin pigmentation variation. M-Index was not associated with serum 25(OH)D concentrations, but the Genetic Score was significantly associated with vitamin D deficiency (serum 25(OH)D levels less than 12 ng/mL) (OR, 1.30; 95% CI, 1.04-1.64). The findings support the hypothesis suggesting that skin pigmentation evolved responding to increased demand for subcutaneous vitamin D synthesis in high latitude environments.

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Loci associated with skin pigmentation identified in African populations.

Publications

Loci associated with skin pigmentation identified in African populations.

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