Relationships between accelerometer-measured and multiple sclerosis: a 2-sample Mendelian randomization study.

Area of Science:

• Genetics
• Epidemiology
• Neurology

Background:

• Observational studies indicate a potential link between physical activity (PA) and a modified risk of developing multiple sclerosis (MS).
• The causal relationship between PA and MS risk remains unclear, necessitating robust investigation.

Purpose of the Study:

• To investigate the potential causal effect of physical activity (PA) on the risk of developing multiple sclerosis (MS).
• Utilize Mendelian randomization (MR) approaches for a robust assessment of causality.

Main Methods:

• Genome-wide association study (GWAS) data from 91,105 UK Biobank participants identified 5 single-nucleotide polymorphisms (SNPs) associated with accelerometer-measured PA.
• Summary-level MS data from a meta-analysis of 14,802 cases and 26,703 controls were used.
• Mendelian randomization analyses were conducted using inverse-variance-weighted, weighted median, and MR-PRESSO methods, with MR-Egger intercept and Cochran's Q statistic for pleiotropy and heterogeneity assessment.

Main Results:

• No statistically significant causal effect of PA on MS risk was detected using the random-effects inverse-variance-weighted method (OR, 0.60; 95% CI, 0.30-1.20; P=0.15).
• Consistent findings were observed across additional MR methods, reinforcing the primary result.
• MR-Egger regression indicated no significant horizontal pleiotropy (Intercept=0.14, P=0.21), and low heterogeneity was present among the SNPs (I²=29.8%, P=0.22).

Conclusions:

• The study suggests that increasing physical activity may not independently alter the risk of developing multiple sclerosis.
• Genetic evidence does not support a causal role for physical activity in modifying MS risk, independent of other known factors.