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

• Verfasst von: Jiang, Xia [VerfasserIn]
• Verfasst von: Kleber, Marcus E. [VerfasserIn]
• Verfasst von: März, Winfried [VerfasserIn]
• Titel: Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
• Verf.angabe: Xia Jiang et al.
• E-Jahr: 2018
• Jahr: 17 January 2018
• Umfang: 12 S.
• Fussnoten: Gesehen am 05.09.2019
• Titel Quelle: Enthalten in: Nature Communications
• Ort Quelle: [London] : Springer Nature, 2010
• Jahr Quelle: 2018
• Band/Heft Quelle: 9(2018) Artikel-Nummer 260, 12 Seiten
• ISSN Quelle: 2041-1723
• DOI: doi:10.1038/s41467-017-02662-2
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1676044590

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 = 4.7x10-9 at rs8018720 in SEC23A, and P = 1.9x10-14 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.