Genome-wide association study of selenium concentrations
Year: 2014
Type: review
Study design: Observational Study
Abstract: 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 × 10(-16)), the same locus identified in the published GWAS of blood Se based on independent cohorts. The lead single-nucleotide polymorphism (SNP) explained ∼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 × 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.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddu546
Institutions: Harvard University, The University of Texas Health Science Center at Houston, Indiana University Bloomington, Indiana University, University of Missouri, Brigham and Women's Hospital, University of North Carolina at Chapel Hill, University of North Carolina Health Care, Tufts University
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: green
Funders: American Diabetes Association, Northwestern University, University of Minnesota, Johns Hopkins University, National Institutes of Health, Centers for Disease Control and Prevention, U.S. Public Health Service, Kaiser Foundation Research Institute, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1141534940, A PROSPECTIVE STUDY OF DIET AND CANCER IN WOMEN, Mercury, Selenium, and Risk of Cardiovascular Disease in Women and Men, G1774001260, G202194050, G2057055131, G261675466, G2670914221, Inflammation and Colorectal Neoplasia, Identity and Function of Selenoprotein Genes, Genes and Environment Initiatives in Type 2 Diabetes, Trace Elements and Cardiovascular Disease (CVD) Risks Factors Among Young Adults, Selenoproteins as targets for cancer prevention, Biochemical and Genetic Markers of Type 2 Diabetes Risk, G316474162, Dietary Etiologies of Heart Disease, Dietary and Hormonal Determinants of Cancer in Women, G3984593164, G405311360, G43250720, GWAS of longitudinal blood pressure profiles from young adulthood to middle-age, NIAMS Multidisciplinary Clin Res Ctr: Rheumatic Diseases, Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3, MULTIPURPOSE ARTHRITIS &MUSCULOSKELETAL DISEASES CENTER, Genes of the CYP450-Derived Eicosanoids Pathway in Subclinical Atherosclerosis, G8990698190, G970283173
OpenAlex ID: W2102583984