Cross-ancestry analyses identify new genetic loci associated with 25-hydroxyvitamin D

by Xiaotong Wang, Valentin Hivert, Shiane Groot, Ying Wang, Loic Yengo, John J. McGrath, Kathryn E. Kemper, Peter M. Visscher, Naomi R. Wray, Joana A. Revez Vitamin D status –a complex trait influenced by environmental and genetic factors–is tightly associated with skin colour and ancestry. Yet very few studies have investigated the genetic underpinnings of vitamin D levels across diverse ancestries, and the ones that have, relied on small sample sizes, resulting in inconclusive results. Here, we conduct genome-wide association studies (GWAS) of 25 hydroxyvitamin D (25OHD)–the main circulating form of vitamin D–in 442,435 individuals from four broad genetically-determined ancestry groups represented in the UK Biobank: European (N = 421,867), South Asian (N = 9,983), African (N = 8,306) and East Asian (N = 2,279). We identify a new genetic determinant of 25OHD (rs146759773) in individuals of African ancestry, which was not detected in previous analysis of much larger European cohorts due to low minor allele frequency. We show genome-wide significant e vidence of dominance effects in 25OHD that protect against vitamin D deficiency. Given that key events in the synthesis of 25OHD occur in the skin and are affected by pigmentation levels, we conduct GWAS of 25OHD stratified by skin colour and identify new associations. Lastly, we test the interactio n between skin colour and variants associated with variance in 25OHD levels and identify two loci (rs10832254 and rs1352846...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research