Genome-wide association study of vitamin D status in diverse ancestry individuals with adjustment for ambient ultraviolet B (UVB) radiation

Background & aim

25-hydroxyvitamin D (25OHD) level, the vitamin D status biomarker, is influenced by genetic and environmental factors, most notably, sun exposure. Additionally, skin pigmentation modifies the amount of ultraviolet radiation that penetrates the skin to initiate vitamin D synthesis. The aim of this study was to identify genetic loci associated with 25OHD among African and Asian ancestry individuals, adjusting for its key environmental determinant, ambient ultraviolet radiation B (UVB).

Methods

A cumulative and weighted UVB dose was estimated for each participant based on their residential area and date of assessment. We performed a genome-wide association study (GWAS) adjusted for age, sex, vitamin D supplement and oily fish intake, principal components, and UVB dose in Central South Asian (CSA, N = 7,497), East Asian (EAS, N = 2,371), and African (AFR, N = 5,637) participants. We also performed a genome-wide variance quantitative trait locus (vQTL) test, adjusted for age, sex, supplement use, oily fish intake, and principal components.

Results

GWAS and vQTL signals were identified in the EAS sample: rs1352846 in the GC gene and rs7775087 in the KCNQ5 gene, respectively. We also replicated previous findings in AFR and CSA samples, rs4588 in GC for both. The significant locus from EAS and a suggestive locus in the MTMR2 gene from CSA show evidence of interaction with ambient UVB.

Conclusion

In this study of individuals of African- and Asian-ancestry, we identified the GC locus, previously primarily associated with vitamin D status in European-ancestry populations, as well as novel loci unique to these ancestries. These findings highlight both shared and ancestry-specific genetic contributions to vitamin D status and underscore the importance of conducting large-scale genetic studies in diverse populations.