维生素D结合蛋白
全基因组关联研究
单核苷酸多态性
维生素D与神经学
祖先信息标记
等位基因
遗传关联
维生素D缺乏
表达数量性状基因座
SNP公司
人口
生物
遗传学
内科学
医学
基因型
基因
环境卫生
作者
Lisa A. Parlato,Rene Welch,Irene M. Ong,Jirong Long,Qiuyin Cai,Mark Steinwandel,William J. Blot,Wei Zheng,Shaneda Warren Andersen
标识
DOI:10.1016/j.ajcnut.2022.12.001
摘要
Vitamin D deficiency is more common among African-ancestry individuals and may be associated with adverse health outcomes. Vitamin D binding protein (VDBP) regulates concentrations of biologically active vitamin D.We conducted genome-wide association study (GWAS) of VDBP and 25-hydroxyvitamin D among African-ancestry individuals.Data were collected from 2,602 African American adults from the Southern Community Cohort Study (SCCS) and 6,934 African- or Caribbean-ancestry adults from the UK Biobank. Serum VDBP concentrations were available only in the SCCS and were measured by using the Polyclonal Human VDBP ELISA kit. Serum 25-hydroxyvitamin D concentrations for both study samples were measured by using Diasorin Liason, a chemiluminescent immunoassay. Participants were genotyped for single nucleotide polymorphisms (SNPs) with genome-wide coverage by using Illumina or Affymetrix platforms. Fine-mapping analysis was performed by using forward stepwise linear regression models including all variants with P value < 5 × 10-8 and within 250 kbps of a lead SNP.We identified 4 loci notably associated with VDBP concentrations in the SCCS population: rs7041 (per allele β = 0.61 μg/mL, SE = 0.05, P = 1.4 × 10-48) and rs842998 (per allele β = 0.39 μg/mL, SE = 0.03, P = 4.0 × 10-31) in GC, rs8427873 (per allele β = 0.31 μg/mL, SE = 0.04, P = 3.0 × 10-14) near GC and rs11731496 (per allele β = 0.21 μg/mL, SE = 0.03, P = 3.6 × 10-11) in between GC and NPFFR2. In conditional analyses, which included the above-mentioned SNPs, only rs7041 remained notable (P = 4.1 × 10-21). SNP rs4588 in GC was the only GWAS-identified SNP associated with 25-hydroxyvitamin D concentration. Among UK Biobank participants: per allele β = -0.11 μg/mL, SE = 0.01, P = 1.5 × 10-13; in the SCCS: per allele β = -0.12 μg/mL, SE = 0.06, P = 2.8 × 10-02). rs7041 and rs4588 are functional SNPs that influence the binding affinity of VDBP to 25-hydroxyvitamin D.Our results were in line with previous studies conducted in European-ancestry populations, showing that GC, the gene that directly encodes for VDBP, would be important for VDBP and 25-hydroxyvitamin D concentrations. The current study extends our knowledge of the genetics of vitamin D in diverse populations.
科研通智能强力驱动
Strongly Powered by AbleSci AI