Gene

Biology

Candidate gene

Endocrinology

Mendelian randomization

Mendelian inheritance

Single-nucleotide polymorphism

Genetics

Bioinformatics

Genome-wide association study

Genetic association

Genotype

Vitamin D and neurology

Genetic variants

Phenotype

Nature Communications

Vitamin D deficiency is a candidate risk factor for a range of adverse health outcomes. In a genome-wide association study of 25 hydroxyvitamin D (25OHD) concentration in 417,580 Europeans we identify 143 independent loci in 112 1-Mb regions, providing insights into the physiology of vitamin D and implicating genes involved in lipid and lipoprotein metabolism, dermal tissue properties, and the sulphonation and glucuronidation of 25OHD. Mendelian randomization models find no robust evidence that 25OHD concentration has causal effects on candidate phenotypes (e.g. BMI, psychiatric disorders), but many phenotypes have (direct or indirect) causal effects on 25OHD concentration, clarifying the epidemiological relationship between 25OHD status and the health outcomes examined in this study.

Genome-wide association study identifies 143 loci associated with 25 hydroxyvitamin D concentration