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Genome-Wide Association Study of Serum Selenium Concentrations
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Department of Biostatistics, University of Washington, Seattle, WA 98195, USA
Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA
Department of Pharmacy, University of Copenhagen, Copenhagen, DK-2100, Denmark
Translational Genomics Research Institute, Phoenix, AZ 85004, USA
Stephens and Associates, Carrollton, TX 75006, USA
Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD 20892, USA
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
Center for Primary Care and Prevention, Memorial Hospital of Rhode Island, Pawtucket, RI 02860, USA
Department of Health Behavior, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA 98195, USA
* Author to whom correspondence should be addressed.
Received: 2 February 2013; in revised form: 2 May 2013 / Accepted: 9 May 2013 / Published: 21 May 2013
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.
Keywords: selenium; serum; selenoprotein; genome-wide association study; AGA; NEIL3; SLC39A11
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Gong, J.; Hsu, L.; Harrison, T.; King, I.B.; Stürup, S.; Song, X.; Duggan, D.; Liu, Y.; Hutter, C.; Chanock, S.J.; Eaton, C.B.; Marshall, J.R.; Peters, U. Genome-Wide Association Study of Serum Selenium Concentrations. Nutrients 2013, 5, 1706-1718.
Gong J, Hsu L, Harrison T, King IB, Stürup S, Song X, Duggan D, Liu Y, Hutter C, Chanock SJ, Eaton CB, Marshall JR, Peters U. Genome-Wide Association Study of Serum Selenium Concentrations. Nutrients. 2013; 5(5):1706-1718.
Gong, Jian; Hsu, Li; Harrison, Tabitha; King, Irena B.; Stürup, Stefan; Song, Xiaoling; Duggan, David; Liu, Yan; Hutter, Carolyn; Chanock, Stephen J.; Eaton, Charles B.; Marshall, James R.; Peters, Ulrike. 2013. "Genome-Wide Association Study of Serum Selenium Concentrations." Nutrients 5, no. 5: 1706-1718.