Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

Nat Commun. 2018 Jan 17;9(1):260. doi: 10.1038/s41467-017-02662-2.

Abstract

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

MeSH terms

  • Amidohydrolases / genetics
  • Autoimmune Diseases / genetics
  • Cohort Studies
  • European Continental Ancestry Group / genetics*
  • Female
  • Genome-Wide Association Study
  • Humans
  • Male
  • Polymorphism, Single Nucleotide
  • Vesicular Transport Proteins / genetics*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood

Substances

  • SEC23A protein, human
  • Vesicular Transport Proteins
  • Vitamin D
  • 25-hydroxyvitamin D
  • Amidohydrolases

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