Genome-wide association study of selenium concentrations

Marilyn C. Cornelis*, Myriam Fornage, Millennia Foy, Pengcheng Xun, Vadim N. Gladyshev, Steve Morris, Daniel I. Chasman, Frank B. Hu, Eric B. Rimm, Peter Kraft, Joanne M. Jordan, Dariush Mozaffarian, Ka He

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Scopus citations

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 fromfour US cohorts. Toenail Sewas 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.

Original languageEnglish (US)
Pages (from-to)1469-1477
Number of pages9
JournalHuman molecular genetics
Volume24
Issue number5
DOIs
StatePublished - Mar 1 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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