Genetically determined selenium concentrations and risk of autoimmune diseases
Ding Ye Nutrition Available online 24 June 2021, 111391
Highlights
• Suggestive evidence supports the causal association between selenium and risk of systemic lupus erythematosus (SLE).
• There is null association between selenium and risk of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD).
• Further work is warranted to clarify the underlying mechanism of selenium in the pathogenesis of SLE.
Objective
: Observational epidemiological studies have reported a relationship between selenium status and risk of autoimmune diseases. However, the associations are susceptible to confounding or reverse causality. Thus, we aimed to investigate the potential causal associations of selenium concentrations with the risk of common autoimmune diseases using a two-sample Mendelian randomization (MR) design.
Methods
: A meta-analysis of genome-wide association studies (GWASs) of selenium among 9,639 individuals of European ancestry was used to identify genetic instruments. Summary statistics of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) were obtained from publicly available GWASs, respectively. We conducted Mendelian randomization (MR) study using the inverse-variance weighted (IVW) 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 (PRESSO) test was used to identify outlier single nucleotide polymorphisms (SNPs).
Results
: Genetically predicted high selenium level was associated with a decreased risk of SLE (odds ratio (OR) 0.85, 95% confidence interval (CI) 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 SNPs were detected (All P > 0.05). However, genetically determined selenium concentrations may be not associated with risk of RA or IBD in the primary analysis and subsequent sensitivity analyses.
Conclusions
: Our study suggested a protective role of selenium on the risk of SLE. Further studies are warranted to elucidate the underlying mechanisms.
