Genetically determined selenium concentrations and risk for autoimmune diseases.

ABSTRACT

OBJECTIVE: Observational epidemiologic studies have reported a relationship between selenium status and risk for autoimmune diseases. However, the associations are susceptible to confounding or reverse causality. Thus, the aim of this study was to investigate the potential causal associations of selenium concentrations with the risk for common autoimmune diseases using a two-sample Mendelian randomization (MR) design. METHODS: A meta-analysis of genome-wide association studies (GWASs) of selenium among 9639 individuals of European ancestry was used to identify genetic instruments. Summary statistics of systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease were obtained from publicly available GWASs, respectively. We conducted MR study using the inverse-variance weighted method, supplemented with weighted median and likelihood-based methods as sensitivity analysis. Cochran Q test and MR-Egger regression were used to detect heterogeneity and potential directional pleiotropy. MR-Pleiotropy RESidual Sum and Outlier test was used to identify outlier single-nucleotide polymorphisms. RESULTS: Genetically predicted high selenium level was associated with a decreased risk for SLE (odds ratio, 0.85; 95% confidence interval, 0.77-0.93; P = 0.001) per natural log-transformed selenium concentrations, with similar results in sensitivity analyses. No evidence of heterogeneity, pleiotropy, or outlier single-nucleotide polymorphisms were detected (all P > 0.05). However, genetically determined selenium concentrations may be not associated with risk for rheumatoid arthritis or inflammatory bowel disease in the primary analysis and subsequent sensitivity analyses. CONCLUSIONS: The present study suggested a protective role of selenium on the risk for systemic lupus erythematosus. Further studies are warranted to elucidate the underlying mechanisms.