Serum Creatinine Protects Against Amyotrophic Lateral Sclerosis: a Mendelian Randomization Study

Association between serum creatinine (sCr) and amyotrophic lateral sclerosis (ALS) has been reported in previous observational studies, but results are at risk of confounding bias and reverse causation. Therefore, whether such association is casual remains unclear. Herein, we performed a two-sample Mendelian randomization study to evaluate the causal relationship between sCr and ALS in both European and East Asian populations. Our analysis was conducted using summary statistics from genome-wide association studies with 358,072 individuals for sCr and 80,610 individuals for ALS in European population, and 142,097 individuals for sCr and 4,084 individuals for ALS in East Asian population. The inverse-variance weighted method was used to estimate the casual-effect of sCr on ALS in both populations, and other MR methods were also performed as sensitivity analyses. We found evidence that genetically predicted sCr was inversely associated with risk of ALS (OR, 0.92; 95% CI, 0.85-0.99; P = 0.028) in European population. However, there was no strong evidence for a causal relationship between sCr and ALS in East Asian population (OR, 0.92; 95% CI, 0.84-1.01; P = 0.084). This study provides evidence that sCr protects against ALS in European population but not in East Asian population.