TY - JOUR
T1 - Common vitamin D pathway gene variants reveal contrasting effects on serum vitamin D levels in African Americans and European Americans
AU - Batai, Ken
AU - Murphy, Adam B.
AU - Shah, Ebony
AU - Ruden, Maria
AU - Newsome, Jennifer
AU - Agate, Sara
AU - Dixon, Michael A.
AU - Chen, Hua Yun
AU - Deane, Leslie A.
AU - Hollowell, Courtney M.P.
AU - Ahaghotu, Chiledum
AU - Kittles, Rick A.
N1 - Funding Information:
Acknowledgments We are grateful to all individuals who participated as research subjects in this study. The authors would also like to thank the urologists and clinic staff at all the participating sites, and Dr. Nathan Ellis for helpful discussion and manuscript edits. This work was supported by grants from the National Institutes of Health (1R01MD007105-01) and the United States Department of Defense (W81XWH-10-1-0532; DAMD W81XWH-07-1-0203). KB was supported by the NCI Training Program: Cancer Education and Career Development Program (5R25 CA057699).
Publisher Copyright:
© 2014, The Author(s).
PY - 2014/10/4
Y1 - 2014/10/4
N2 - Vitamin D deficiency is more common among African Americans (AAs) than among European Americans (EAs), and epidemiologic evidence links vitamin D status to many health outcomes. Two genome-wide association studies (GWAS) in European populations identified vitamin D pathway gene single-nucleotide polymorphisms (SNPs) associated with serum vitamin D [25(OH)D] levels, but a few of these SNPs have been replicated in AAs. Here, we investigated the associations of 39 SNPs in vitamin D pathway genes, including 19 GWAS-identified SNPs, with serum 25(OH)D concentrations in 652 AAs and 405 EAs. Linear and logistic regression analyses were performed adjusting for relevant environmental and biological factors. The pattern of SNP associations was distinct between AAs and EAs. In AAs, six GWAS-identified SNPs in GC, CYP2R1, and DHCR7/NADSYN1 were replicated, while nine GWAS SNPs in GC and CYP2R1 were replicated in EAs. A CYP2R1 SNP, rs12794714, exhibited the strongest signal of association in AAs. In EAs, however, a different CYP2R1 SNP, rs1993116, was the most strongly associated. Our models, which take into account genetic and environmental variables, accounted for 20 and 28 % of the variance in serum vitamin D levels in AAs and EAs, respectively.
AB - Vitamin D deficiency is more common among African Americans (AAs) than among European Americans (EAs), and epidemiologic evidence links vitamin D status to many health outcomes. Two genome-wide association studies (GWAS) in European populations identified vitamin D pathway gene single-nucleotide polymorphisms (SNPs) associated with serum vitamin D [25(OH)D] levels, but a few of these SNPs have been replicated in AAs. Here, we investigated the associations of 39 SNPs in vitamin D pathway genes, including 19 GWAS-identified SNPs, with serum 25(OH)D concentrations in 652 AAs and 405 EAs. Linear and logistic regression analyses were performed adjusting for relevant environmental and biological factors. The pattern of SNP associations was distinct between AAs and EAs. In AAs, six GWAS-identified SNPs in GC, CYP2R1, and DHCR7/NADSYN1 were replicated, while nine GWAS SNPs in GC and CYP2R1 were replicated in EAs. A CYP2R1 SNP, rs12794714, exhibited the strongest signal of association in AAs. In EAs, however, a different CYP2R1 SNP, rs1993116, was the most strongly associated. Our models, which take into account genetic and environmental variables, accounted for 20 and 28 % of the variance in serum vitamin D levels in AAs and EAs, respectively.
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U2 - 10.1007/s00439-014-1472-y
DO - 10.1007/s00439-014-1472-y
M3 - Article
C2 - 25085266
AN - SCOPUS:84919413313
VL - 133
SP - 1395
EP - 1405
JO - Human Genetics
JF - Human Genetics
SN - 0340-6717
IS - 11
ER -