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

Area of Science:

• Genetics
• Neurology
• Biochemistry

Background:

• Observational studies suggest a link between serum creatinine (sCr) and amyotrophic lateral sclerosis (ALS), but are limited by confounding and reverse causation.
• The causal nature of the association between sCr and ALS remains uncertain.

Purpose of the Study:

• To investigate the potential causal relationship between genetically predicted serum creatinine levels and the risk of developing amyotrophic lateral sclerosis.
• To examine this relationship in both European and East Asian populations.

Main Methods:

• A two-sample Mendelian randomization study design was employed.
• Genome-wide association study summary statistics from large cohorts were utilized for sCr and ALS in European and East Asian populations.
• Inverse-variance weighted method and other sensitivity analyses were performed to assess causality.

Main Results:

• In the European population, genetically predicted sCr showed an inverse association with ALS risk (OR, 0.92; 95% CI, 0.85-0.99; P = 0.028).
• In the East Asian population, no significant causal relationship was observed between sCr and ALS risk (OR, 0.92; 95% CI, 0.84-1.01; P = 0.084).

Conclusions:

• Serum creatinine may have a protective effect against amyotrophic lateral sclerosis in the European population.
• The study did not find evidence for a causal effect of sCr on ALS in the East Asian population, suggesting potential population-specific differences.