Title | Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Jiang X, O'Reilly PF, Aschard H, et al. |
Secondary Authors | Kiel DP |
Journal | Nat Commun |
Volume | 9 |
Issue | 1 |
Pagination | 260 |
Date Published | 2018 01 17 |
ISSN | 2041-1723 |
Keywords | Amidohydrolases, Autoimmune Diseases, Cohort Studies, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Vesicular Transport Proteins, Vitamin D |
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 at rs8018720 in SEC23A, and P = 1.9×10 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. |
DOI | 10.1038/s41467-017-02662-2 |
Alternate Journal | Nat Commun |
PubMed ID | 29343764 |
PubMed Central ID | PMC5772647 |
Grant List | MC_UU_00007/1 / MRC_ / Medical Research Council / United Kingdom G1001799 / MRC_ / Medical Research Council / United Kingdom MR/N01104X/2 / MRC_ / Medical Research Council / United Kingdom MR/N003284/1 / MRC_ / Medical Research Council / United Kingdom 12-1087 / AICR_ / Worldwide Cancer Research / United Kingdom G1000143 / MRC_ / Medical Research Council / United Kingdom R01 AR072199 / AR / NIAMS NIH HHS / United States MR/N01104X/1 / MRC_ / Medical Research Council / United Kingdom P30 DK063491 / DK / NIDDK NIH HHS / United States MC_PC_U127561128 / MRC_ / Medical Research Council / United Kingdom MC_UU_12015/5 / MRC_ / Medical Research Council / United Kingdom G0600329 / MRC_ / Medical Research Council / United Kingdom MR/N015746/1 / MRC_ / Medical Research Council / United Kingdom MC_PC_U127527198 / MRC_ / Medical Research Council / United Kingdom 12076 / CRUK_ / Cancer Research UK / United Kingdom G0601653 / MRC_ / Medical Research Council / United Kingdom RG/08/014/24067 / BHF_ / British Heart Foundation / United Kingdom MR/L003120/1 / MRC_ / Medical Research Council / United Kingdom R01 AR041398 / AR / NIAMS NIH HHS / United States MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom MC_U127527198 / MRC_ / Medical Research Council / United Kingdom K01 DK109019 / DK / NIDDK NIH HHS / United States PHCS/C4/4/016 / DH_ / Department of Health / United Kingdom 14136 / CRUK_ / Cancer Research UK / United Kingdom G0401527 / MRC_ / Medical Research Council / United Kingdom MR/K018647/1 / MRC_ / Medical Research Council / United Kingdom G0600237 / MRC_ / Medical Research Council / United Kingdom UL1 TR001881 / TR / NCATS NIH HHS / United States PG/09/023/26806 / BHF_ / British Heart Foundation / United Kingdom |