Journal
HUMAN MOLECULAR GENETICS
Volume 24, Issue 5, Pages 1469-1477Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddu546
Keywords
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Funding
- National Cancer Institute (NCI) [P01CA087969, R01CA137178]
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01DK058845]
- National Heart, Lung, and Blood Institute (NHLBI) [R01HL35464]
- Gene Environment-Association Studies (GENEVA) project under the NIH Genes, Environment, and Health Initiative [U01HG004399]
- Merck/Rosetta Research Laboratories, North Wales, PA
- National Heart, Lung, and Blood Institute (NHLBI)
- University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]
- Northwestern University [HHSN268201300027C]
- University of Minnesota [HHSN268201300028C]
- Kaiser Foundation Research Institute [HHSN268201300029C]
- Johns Hopkins University School of Medicine [HHSN268200900041C]
- National Institute on Aging (NIA)
- NIA
- NHLBI [AG0005, R01-HL-084099, R01HL081572]
- National Human Genome Research Institute [U01-HG-004729]
- Association of Schools of Public Health
- Centers for Disease Control and Prevention [S043, S1733, S3486]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [P60-AR30701, P-60-AR49465]
- Algynomics, Inc.
- American Diabetes Association [7-13-JF-15]
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Selenium (Se) is an essential trace element in human nutrition, but its role in certain health conditions, particularly among Se sufficient populations, is controversial. A genome-wide association study (GWAS) of blood Se concentrations previously identified a locus at 5q14 near BHMT. We performed a GW meta-analysis of toenail Se concentrations, which reflect a longer duration of exposure than blood Se concentrations, including 4162 European descendants from four US cohorts. Toenail Se was measured using neutron activation analysis. We identified a GW-significant locus at 5q14 (P < 1 x 10(-16)), the same locus identified in the published GWAS of blood Se based on independent cohorts. The lead single-nucleotide polymorphism (SNP) explained similar to 1% of the variance in toenail Se concentrations. Using GW-summary statistics from both toenail and blood Se, we observed statistical evidence of polygenic overlap (P < 0.001) and meta-analysis of results from studies of either trait (n = 9639) yielded a second GW-significant locus at 21q22.3, harboring CBS (P < 4 x 10(-8)). Proteins encoded by genes at 5q14 and 21q22.3 function in homocysteine (Hcy) metabolism, and index SNPs for each have previously been associated with betaine and Hcy levels in GWAS. Our findings show evidence of a genetic link between Se and Hcy pathways, both involved in cardiometabolic disease.
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