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

Autoři: Ken Batai aff001;  Zuxi Cui aff002;  Amit Arora aff003;  Ebony Shah-Williams aff004;  Wenndy Hernandez aff005;  Maria Ruden aff006;  Courtney M. P. Hollowell aff006;  Stanley E. Hooker aff007;  Madhavi Bathina aff007;  Adam B. Murphy aff008;  Carolina Bonilla aff009;  Rick A. Kittles aff007
Působiště autorů: Department of Urology, University of Arizona, Tucson, Arizona, United States of America aff001;  Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, United States of America aff002;  Department of Epidemiology and Biostatistics, University of Arizona, Tucson, Arizona, United States of America aff003;  Department of Medical and Molecular Genetics, Indiana University, Indianapolis, Indiana United States of America aff004;  Department of Medicine, University of Chicago, Chicago, Illinois, United States of America aff005;  Department of Surgery, Cook County Health and Hospitals System, Chicago, Illinois, United States of America aff006;  Division of Health Equities, Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, California, United States of America aff007;  Department of Urology, Northwestern University, Chicago, Illinois, United States of America aff008;  Departamento de Medicina Preventiva, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil aff009;  Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom aff010
Vyšlo v časopise: Genetic loci associated with skin pigmentation in African Americans and their effects on vitamin D deficiency. PLoS Genet 17(2): e1009319. doi:10.1371/journal.pgen.1009319
Kategorie: Research Article


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.

Klíčová slova:

vitamín D – Genetic loci – Genetics – Genome-wide association studies – Genomics – Human genetics – Single nucleotide polymorphisms – Vitamin D deficiency


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