Genetic loci associated with skin pigmentation in African Americans and their effects on vitamin D deficiency
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 theSLC24A5gene (rs2675345) showed the strongest signal of association with M-Index (P= 4.0 x 10−30in the pooled dataset). Variants inSLC24A5,SLC45A2andOCA2together account for a large proportion of skin pigmentation variance (11%). The effects of these variants on M-Index was modified by sex (Pfor 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 18, 2021
- Source ID
- 10.1371/journal.pgen.1009319
Entities
People
- Adam B Murphy
- Amit Arora
- Carolina Bonilla
- Courtney M.P. Hollowell
- Ebony Shah-williams
- Ken Batai
- Madhavi Bathina
- Maria Ruden
- Rick Kittles
- Stanley Hooker
- Wenndy Hernandez
- Zuxi Cui
Organizations
- National Institute on Minority Health and Health Disparities
- United States Department of Defense