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Genome-wide association study of circulating vitamin D levels
Ahn, Jiyoung2; Yu, Kai; Stolzenberg-Solomon, Rachael; Simon, K. Claire3; McCullough, Marjorie L.6; Gallicchio, Lisa7; Jacobs, Eric J.6; Ascherio, Alberto3,4,8,9; Helzlsouer, Kathy7; Jacobs, Kevin B.; Li, Qizhai10; Weinstein, Stephanie J.; Purdue, Mark; Virtamo, Jarmo11; Horst, Ronald12; Wheeler, William13; Chanock, Stephen; Hunter, David J.3,4,5; Hayes, Richard B.2; Kraft, Peter4,5; Albanes, Demetrius1
AbstractThe 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 x 10(-30)), in linkage disequilibrium (LD) with rs7041, a non-synonymous SNP (D432E; P = 4.1 x 10(-22)) and rs1155563 (P = 3.8 x 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 x 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 x 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 D(3) to an active vitamin D receptor ligand; P = 1.4 x 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 x 10(-49)), NADSYN1/DHCR7 (P = 3.4 x 10(-9)) and CYP2R1 (P = 2.9 x 10(-17)), but not C10orf88 (P = 2.4 x 10(-5)).
Funding ProjectNational Cancer Institute, NIH[N01-CO-12400] ; US Public Health Service[N01-CN-45165] ; US Public Health Service[N01-RC45035] ; US Public Health Service[N01-RC-37004] ; National Cancer Institute, NIH, DHHS[HHSN261201000006C] ; Division of Cancer Epidemiology and Genetics ; Division of Cancer Prevention ; National Cancer Institute (NCI) ; US National Institutes of Health (NIH) ; Department of Health and Human Services (DHHS) ; NIH[P01CA087969] ; NIH[5U01HG004399-2] ; NIH[P01CA055075] ; NIH Kirschstein-NRSA[T32 ES016645-01] ; [U01 CA098710]
WOS Research AreaBiochemistry & Molecular Biology ; Genetics & Heredity
WOS SubjectBiochemistry & Molecular Biology ; Genetics & Heredity
WOS IDWOS:000279674200018
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Document Type期刊论文
Corresponding AuthorAlbanes, Demetrius
Affiliation1.NCI, Div Canc Epidemiol & Genet, EPS 320, NIH, Bethesda, MD 20892 USA
2.NYU, Sch Med, Dept Environm Med, Div Epidemiol, New York, NY 10016 USA
3.Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA
4.Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA
5.Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA
6.Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30303 USA
7.Mercy Med Ctr, Weinberg Ctr Womens Hlth & Med, Prevent & Res Ctr, Baltimore, MD 21202 USA
8.Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA
9.Harvard Univ, Sch Med, Boston, MA USA
10.Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst & Control, Beijing, Peoples R China
11.Natl Inst Hlth & Welf, Dept Chron Dis Prevent, FI-00271 Helsinki, Finland
12.Heartland Assays Inc, Ames, IA USA
13.Informat Management Serv Inc, Rockville, MD USA
Recommended Citation
GB/T 7714
Ahn, Jiyoung,Yu, Kai,Stolzenberg-Solomon, Rachael,et al. Genome-wide association study of circulating vitamin D levels[J]. HUMAN MOLECULAR GENETICS,2010,19(13):2739-2745.
APA Ahn, Jiyoung.,Yu, Kai.,Stolzenberg-Solomon, Rachael.,Simon, K. Claire.,McCullough, Marjorie L..,...&Albanes, Demetrius.(2010).Genome-wide association study of circulating vitamin D levels.HUMAN MOLECULAR GENETICS,19(13),2739-2745.
MLA Ahn, Jiyoung,et al."Genome-wide association study of circulating vitamin D levels".HUMAN MOLECULAR GENETICS 19.13(2010):2739-2745.
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