Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels.
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Peer-reviewed
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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.
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2041-1723
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Medical Research Council (MC_UU_12015/5)
Medical Research Council (G1000143)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research Uk (None)
Medical Research Council (G0401527)
Cancer Research Uk (None)
MRC (MC_PC_13048)
Department of Health (via National Institute for Health Research (NIHR)) (unknown)
National Institute for Health Research (NIHR) (NF-SI-0512-10114)
Medical Research Council (MR/L003120/1)
Medical Research Council (MR/N003284/1)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
British Heart Foundation (None)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (701708)
Medical Research Council (G0401527/1)
Medical Research Council (MC_PC_13048)