Genome-wide association study of circulating vitamin D levels.
Genome-wide association study of circulating vitamin D levels.
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DOI：
10.1093/hmg/ddq155
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发表时间：
2010-07-01
影响因子：
3.5
通讯作者：
Albanes D
中科院分区：
文献类型：
--
作者：
Ahn J;Yu K;Stolzenberg-Solomon R;Simon KC;McCullough ML;Gallicchio L;Jacobs EJ;Ascherio A;Helzlsouer K;Jacobs KB;Li Q;Weinstein SJ;Purdue M;Virtamo J;Horst R;Wheeler W;Chanock S;Hunter DJ;Hayes RB;Kraft P;Albanes D
维生素D的主要循环形式，25-羟基维生素D [25（OH）D]，与多种医学结果相关，包括佝偻病，骨质疏松症，多发性硬化症和癌症。在一项对来自5个队列的4501名欧洲血统的人进行的全基因组关联研究（GWAS）中，我们确定了编码组特异性组分的基因中的单核苷酸多态性（SNP）。（维生素D结合）蛋白，GC，染色体4 q12 -13上与25（OH）D浓度相关：rs 2282679（P = 2.0 × 10−30），与rs7041（非同义SNP; D432 E; P = 4.1 × 10−22）和rs 1155563（P = 3.8 × 10−25）连锁不平衡（LD）。在涉及维生素D合成或激活的其他三个基因中或附近的SNP中也观察到与25（OH）D相关的暗示信号：NADSYN 1中染色体11q13.4上的rs3829251 [编码烟酰胺腺嘌呤二核苷酸（NAD）合成酶; P = 8.8 × 10−7]，与rs 1790349处于高LD，位于DHCR 7，编码7-脱氢胆固醇还原酶的基因，该还原酶从7-脱氢胆固醇合成胆固醇; rs6599638在包含开放阅读框88的区域中（C10 orf 88）位于染色体10q26.13上ACADSB附近（酰基辅酶A脱氢酶），参与胆固醇和维生素D的合成（P = 3.3 × 10−7）;以及CYP 2 R1中染色体11p15.2上的rs 2060793（细胞色素P450，家族2，亚家族R，多肽1，编码将维生素D3转化为活性维生素D受体配体的关键C-25羟化酶; P = 1.4 × 10−5）。我们在另外2221个样本中对这四个区域的SNP进行了基因分型，并通过对GC（P = 1.8 × 10−49）、NADSYN 1/DHCR 7（P = 3.4 × 10−9）和CYP 2 R1（P = 2.9 × 10−17）的GWAS数据进行荟萃分析，证实了与25（OH）D的强全基因组显著关联，但不包括C10 orf 88（P = 2.4 × 10−5）。
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).
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DOI：
10.1016/j.mrfmmm.2005.06.013
发表时间：
2005-12-30
影响因子：
2.3
作者：
Hayes, RB;Sigurdson, A;Berg, CD
通讯作者：
Berg, CD
影响因子：
5.6
作者：
Strushkevich, Naltallia;Usanov, Serge A.;Park, Hee-Won
通讯作者：
Park, Hee-Won
影响因子：
3.8
作者：
Bertone-Johnson, ER;Chen, WY;Hankinson, SE
通讯作者：
Hankinson, SE
DOI：
10.1093/ajcn/88.2.441
发表时间：
2008-08
期刊：
The American journal of clinical nutrition
影响因子：
--
作者：
Orton SM;Morris AP;Herrera BM;Ramagopalan SV;Lincoln MR;Chao MJ;Vieth R;Sadovnick AD;Ebers GC
通讯作者：
Ebers GC
DOI：
10.1073/pnas.0402490101
发表时间：
2004-05-18
影响因子：
11.1
作者：
Cheng, JB;Levine, MA;Russell, DW
通讯作者：
Russell, DW