Details

Autor(en) / Beteiligte

• Ahn, Jiyoung
• Yu, Kai
• Stolzenberg-Solomon, Rachael
• Simon, K. Claire
• McCullough, Marjorie L.
• Gallicchio, Lisa
• Jacobs, Eric J.
• Ascherio, Alberto
• Helzlsouer, Kathy
• Jacobs, Kevin B.
• Li, Qizhai
• Weinstein, Stephanie J.
• Purdue, Mark
• Virtamo, Jarmo
• Horst, Ronald
• Wheeler, William
• Chanock, Stephen
• Hunter, David J.
• Hayes, Richard B.
• Kraft, Peter
• Albanes, Demetrius

Titel

Genome-wide association study of circulating vitamin D levels

Ist Teil von

• Human molecular genetics, 2010-07, Vol.19 (13), p.2739-2745

Ort / Verlag

Oxford: Oxford University Press

Erscheinungsjahr

2010

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• The primary circulating form of vitamin D, 25-hydroxy-vitamin D [25(OH)D], is associated with multiple medical outcomes, including rickets, osteoporosis, multiple sclerosis and cancer. In a genome-wide association study (GWAS) of 4501 persons of European ancestry drawn from five cohorts, we identified single-nucleotide polymorphisms (SNPs) in the gene encoding group-specific component (vitamin D binding) protein, GC, on chromosome 4q12-13 that were associated with 25(OH)D concentrations: rs2282679 (P = 2.0 × 10−30), in linkage disequilibrium (LD) with rs7041, a non-synonymous SNP (D432E; P = 4.1 × 10−22) and rs1155563 (P = 3.8 × 10−25). Suggestive signals for association with 25(OH)D were also observed for SNPs in or near three other genes involved in vitamin D synthesis or activation: rs3829251 on chromosome 11q13.4 in NADSYN1 [encoding nicotinamide adenine dinucleotide (NAD) synthetase; P = 8.8 × 10−7], which was in high LD with rs1790349, located in DHCR7, the gene encoding 7-dehydrocholesterol reductase that synthesizes cholesterol from 7-dehydrocholesterol; rs6599638 in the region harboring the open-reading frame 88 (C10orf88) on chromosome 10q26.13 in the vicinity of ACADSB (acyl-Coenzyme A dehydrogenase), involved in cholesterol and vitamin D synthesis (P = 3.3 × 10−7); and rs2060793 on chromosome 11p15.2 in CYP2R1 (cytochrome P450, family 2, subfamily R, polypeptide 1, encoding a key C-25 hydroxylase that converts vitamin D3 to an active vitamin D receptor ligand; P = 1.4 × 10−5). We genotyped SNPs in these four regions in 2221 additional samples and confirmed strong genome-wide significant associations with 25(OH)D through meta-analysis with the GWAS data for GC (P = 1.8 × 10−49), NADSYN1/DHCR7 (P = 3.4 × 10−9) and CYP2R1 (P = 2.9 × 10−17), but not C10orf88 (P = 2.4 × 10−5).