title: Genome-wide association study of selenium concentrations.
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.
authors.affiliation: Channing Division of Network Medicine, Department of Nutrition, mcorneli@hsph.harvard.edu.
authors.forename: Marilyn C
authors.initials: MC
authors.lastname: Cornelis
authors.affiliation: Center for Human Genetics, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.affiliation: Center for Human Genetics, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Millennia
authors.initials: M
authors.lastname: Foy
authors.affiliation: Department of Epidemiology and Biostatistics, Indiana University at Bloomington, Bloomington, IN, USA.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Xun
authors.affiliation: Division of Genetics and.
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
authors.affiliation: University of Missouri Research Reactor Center, Columbia, MO, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Morris
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.affiliation: Channing Division of Network Medicine, Department of Nutrition, Department of Epidemiology, and.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.affiliation: Channing Division of Network Medicine, Department of Nutrition, Department of Epidemiology, and.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Rimm
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, NC, USA, Department of Medicine and Department of Orthopaedics, UNC School of Medicine, NC, USA, Department of Epidemiology, UNC Gillings School of Global Public Health, NC, USA.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Jordan
authors.affiliation: Channing Division of Network Medicine, Department of Nutrition, Department of Epidemiology, and Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.
authors.forename: Dariush
authors.initials: D
authors.lastname: Mozaffarian
authors.affiliation: Department of Epidemiology and Biostatistics, Indiana University at Bloomington, Bloomington, IN, USA.
authors.forename: Ka
authors.initials: K
authors.lastname: He
mesh_terms: D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D060005:Genotyping Techniques; D006710:Homocysteine / Q000097:blood; D006801:Humans; D009262:Nails / Q000737:chemistry; D020641:Polymorphism, Single Nucleotide; D012643:Selenium / Q000097:blood / Q000737:chemistry*; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism; D054481:Thioredoxin Reductase 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D051140:Selenoproteins; D006710:Homocysteine; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; D012643:Selenium