Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
書誌事項
- 公開日
- 2018-01-17
- 権利情報
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- https://creativecommons.org/licenses/by/4.0
- https://creativecommons.org/licenses/by/4.0
- DOI
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- 10.1038/s41467-017-02662-2
- 公開者
- Springer Science and Business Media LLC
説明
<jats:title>Abstract</jats:title><jats:p>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 (<jats:italic>GC, NADSYN1/DHCR7, CYP2R1, CYP24A1</jats:italic>). 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 (<jats:italic>P</jats:italic> = 4.7×10<jats:sup>−9</jats:sup> at rs8018720 in <jats:italic>SEC23A</jats:italic>, and <jats:italic>P</jats:italic> = 1.9×10<jats:sup>−14</jats:sup> at rs10745742 in <jats:italic>AMDHD1</jats:italic>). 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.</jats:p>
収録刊行物
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- Nature Communications
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Nature Communications 9 (1), 260-, 2018-01-17
Springer Science and Business Media LLC