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Genetic loci associated with skin pigmentation in African Americans and their effects on vitamin D deficiency

Batai, Ken, Cui, Zuxi, Arora, Amit, Shah-Williams, Ebony, Hernandez, Wenndy, Ruden, Maria, Hollowell, Courtney M. P., Hooker, Stanley E., Bathina, Madhavi, Murphy, Adam B., Bonilla, Carolina, Kittles, Rick A.·2021·PLOS Genetics
DOI 10.1371/journal.pgen.1009319PMC PMC7891745
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Abstract

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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Metadata

Authors
Batai, K., Cui, Z., Arora, A., Shah-Williams, E., Hernandez, W., Ruden, M., Hollowell, C. M. P., Hooker, S. E., Bathina, M., Murphy, A. B., Bonilla, C., & Kittles, R. A.
ORCID
Venue
PLOS Genetics
Publisher
Public Library of Science (PLoS)
Published
2021-02-18
Volume
17
Issue
2
Pages
e1009319
ISSN
1553-7404
DOI
10.1371/journal.pgen.1009319
PMC
PMC7891745
Cited by
28
References
14
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • National Institute on Minority Health and Health Disparities (1R01MD007105)
  • U.S. Department of Defense (W81XWH-10-1-0532, DAMD W81XWH-07-1-0203)

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