Genome-Wide Association Study of Serum 25-Hydroxyvitamin D in US Women.

摘要: Genetic factors likely influence individuals' concentrations of 25-hydroxyvitamin D [25(OH)D], a biomarker vitamin exposure previously linked to reduced risk several chronic diseases. We conducted genome-wide association study serum 25(OH)D (assessed using liquid chromatography-tandem mass spectrometry) and 386,449 single nucleotide polymorphisms (SNPs). Our sample consisted 1829 participants randomly selected from the Sister Study, cohort women who had sister with breast cancer but never themselves. 19,741 SNPs were associated (p<0.05). re-assessed these hits in an independent 1534 later developed cancer. After pooling, 32 significant associations (p<5x10-8). These located or near GC, binding protein, CYP2R1, cytochrome P450 enzyme that hydroxylates form 25(OH)D. The top hit was rs4588, missense GC polymorphism 3.5 ng/mL decrease per copy minor allele (95% confidence interval [CI]: -4.1, -3.0; p=4.5x10-38). strongest SNP CYP2R1 rs12794714, synonymous variant (p=3.8x10-12; =1.8 [CI: -2.2, -1.3]). Serum samples collected some 3-10 years after baseline (811 cases, 780 non-cases) also strongly both loci. findings augment our understanding genetic influences on possible role proteins enzymes determining measured levels. results may help identify individuals genetically predisposed insufficiency.