Abstract
INTRODUCTION: Selenium is a trace mineral that is commonly included in micronutrient supplements. The effect of selenium on kidney function remains unclear. A genetically predicted micronutrient and its association with estimated glomerular filtration rate (eGFR) can be used to assess the causal estimates by Mendelian randomization (MR). METHODS: In this MR study, we instrumented 11 genetic variants associated with blood or total selenium levels from a previous genome-wide association study (GWAS). The association between genetically predicted selenium concentration and eGFR was first assessed by summary-level MR in the chronic kidney disease(CKDGen) GWAS meta-analysis summary statistics, including 567,460 European samples. Inverse-variance weighted and pleiotropy-robust MR analyses were performed, in addition to multivariable MR adjusted for the effects of type 2 diabetes mellitus. Replication analysis was performed with individual-level UK Biobank data, including 337,318 White individuals of British ancestry. RESULTS: Summary-level MR analysis indicated that a genetically predicted 1 SD increase in selenium concentration was significantly associated with lower eGFR (-1.05 [-1.28, -0.82] %). The results were similarly reproduced by pleiotropy-robust MR analysis, including MR-Egger and weighted-median methods, and consistent even in the multivariable MR adjusted for diabetes. In the UK Biobank data, genetically predicted higher selenium concentration was also significantly associated with lower eGFR (- 0.36 [-0.52, -0.20] %), and the results were similar when body mass index, waist circumference, hypertension, and diabetes mellitus covariates were adjusted (-0.33 [-0.50, -0.17] %). CONCLUSION: This MR study supports the hypothesis that higher genetically predicted body selenium is causally associated with lower eGFR.