OSBPL11 is an African-specific locus associated with 25-hydroxyvitamin D concentrations and cardiometabolic health

Vitamin D deficiency is prevalent in Africa, but its genetic determinants are understudied. We report a genome-wide analysis of 25-hydroxyvitamin D (25(OH)D) concentrations in 3670 children from five countries across Africa with replication in four diaspora African ancestry populations (n=21,610). We identify a previously unreported locus at genome-wide significance in West African populations: OSBPL11 (Oxysterol Binding Protein Like 11, lead variant, rs2979356, p=8.01 x 10-9). In vitro and molecular docking assays showed that OSBPL11 is a vitamin D binding protein likely involved in the intracellular binding of vitamin D metabolites. OSBPL11 knockdown mice have increased fat, reduced triglycerides and improved glucose tolerance, and rs2979356 was associated with cardiometabolic health in adults of African ancestry. We also identify previously reported loci determining vitamin D status. Our study advances understanding of vitamin D genetics in Africa and indicates a novel function for OSBPL11 in intracellular binding and transport of vitamin D metabolites.