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

TitleGenome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels.
Publication TypeJournal Article
Year of Publication2018
AuthorsJiang X, O'Reilly PF, Aschard H, et al.
Secondary AuthorsKiel DP
JournalNat Commun
Volume9
Issue1
Pagination260
Date Published2018 01 17
ISSN2041-1723
KeywordsAmidohydrolases, 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.

DOI10.1038/s41467-017-02662-2
Alternate JournalNat Commun
PubMed ID29343764
PubMed Central IDPMC5772647
Grant ListMC_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