Genome-Wide Association Study of Serum Selenium Concentrations

Abstract

Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening and the Women’s Health Initiative (WHI). We tested association between 2,474,333 single nucleotide polymorphisms (SNPs) and serum selenium concentrations using linear regression models. In the first stage (PLCO) 41 SNPs clustered in 15 regions had p < 1 × 10−5. None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003) in the second stage (WHI). Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11) and had p between 2.62 × 10−7 and 4.04 × 10−7 in the combined analysis (PLCO + WHI). Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations.

Current State of Evidence: Influence of Nutritional and Nutrigenetic Factors on Immunity in the COVID-19 Pandemic Framework

“…In this context, individuals carrying A alleles for both rs891684 and rs17823744 SNPs are associated with decreased levels of selenium, which could compromise the bioavailability of this micronutrient to circulating immune cells. These two polymorphisms have been most strongly associated with differential levels of selenium in GWAs based on European populations, especially rs891684 located in the SLC39A11 (solute carrier family 39 member 11), a gene that codes for a zinc transporter [30]. On the other hand, rs17823744 is located in the DMGDH gene, which codes for dimethylglycine dehydrogenase (an enzyme involved in the catabolism of choline in the mitochondrial matrix) that uses adenine-flavin dinucleotide and Folate as cofactors, and this SNP is associated with differential levels of selenium in toenails [31], an alternative marker to assess the nutritional status of selenium [150].…”

An Assessment of Serum Selenium Concentration in Women with Ovarian Cancer

“…The relationship between selenium concentration and ovarian cancer seems to be complex and depends not only on the neoplastic process itself and its advancement or nutritional status but also on the influence of other factors, including genetic ones [ 86 , 87 , 88 ]. Selenium itself is also beginning to be seen as a possible component of oncological therapy.…”

Pathogenic Variants in Selenoproteins and Selenocysteine Biosynthesis Machinery

“…Four GWAS on circulating selenium concentrations have been published in recent years [ 77 , 78 , 79 , 80 ]. Perhaps not surprisingly, individual variants in selenoproteins did not reach genome-wide significance levels.…”