Genome-wide association study of selenium concentrations

Area of Science:

• Genetics
• Nutritional Science
• Metabolic Disease Research

Background:

• Selenium (Se) is an essential trace element with a debated role in health, especially in sufficient populations.
• Previous genome-wide association studies (GWAS) linked blood Se concentrations to a locus at 5q14 near BHMT.
• Toenail Se concentrations offer a longer-term exposure measure compared to blood Se.

Purpose of the Study:

• To conduct a genome-wide (GW) meta-analysis of toenail Se concentrations to identify genetic loci.
• To investigate the genetic overlap between toenail and blood Se concentrations.
• To explore the genetic relationship between Se and homocysteine (Hcy) metabolism pathways.

Main Methods:

• Performed a GW meta-analysis of toenail Se concentrations in 4162 European descendants from four US cohorts.
• Measured toenail Se using neutron activation analysis.
• Utilized GW-summary statistics from both toenail and blood Se traits for meta-analysis.

Main Results:

• Identified a GW-significant locus at 5q14 (P < 1 × 10(-16)), consistent with prior blood Se GWAS findings.
• The lead single-nucleotide polymorphism (SNP) at 5q14 explained approximately 1% of toenail Se variance.
• A second GW-significant locus at 21q22.3, near CBS, was identified through meta-analysis of combined Se traits (P < 4 × 10(-8)).
• Observed statistical evidence of polygenic overlap between toenail and blood Se concentrations (P < 0.001).

Conclusions:

• Established a genetic link between Se and Hcy metabolism pathways.
• Genes at the identified loci (5q14 and 21q22.3) are involved in Hcy metabolism.
• Findings suggest a genetic basis for the interplay between Se and Hcy pathways, relevant to cardiometabolic disease.