Related Experiment Video
Updated: Jul 24, 2026
A Method of Trigonometric Modelling of Seasonal Variation Demonstrated with Multiple Sclerosis Relapse Data
Published on: December 9, 2015
Relationships between accelerometer-measured and multiple sclerosis: a 2-sample Mendelian randomization study
Hui Lu1, Peng-Fei Wu2,3, Rui-Zhuo Li4
1Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. erjihuixin@163.com.
Background:
Observational studies suggest that physical activity (PA) can independently modify the risk of developing multiple sclerosis (MS).
Objective:
To investigate the causal effect of PA on MS by Mendelian randomization (MR) approaches.
Methods:
Through a genome-wide association study including 91,105 participants from UK Biobank, we obtained 5 single-nucleotide polymorphisms (SNPs) associated with accelerometer-measured PA (P < 5 × 10-8). Summary-level data for MS were obtained from a meta-analysis, incorporating 14,802 subjects with MS and 26,703 healthy controls of European ancestry. MR analyses were performed using the inverse-variance-weighted method, weighted median estimator, and MR-PRESSO method. Additional analyses were further performed using MR-Egger intercept and Cochran's Q statistic to verify the robustness of our findings.
Results:
We failed to detect a causal effect of PA on MS (OR, 0.60; 95% confidence interval [CI], 0.30-1.20; P = 0.15) per in the random-effects IVW analysis. Additional MR methods yielded consistent results. MR-Egger regression suggested no evidence of horizontal pleiotropy (Intercept = 0.14, P = 0.21) and there seemed no substantial heterogeneity (I2 = 29.8%, P = 0.22) among individual SNPs.
Conclusion:
Our findings suggest that enhancing PA might not modify the risk of developing MS independent of established risk factors.
Insights
Physical activity (PA) does not appear to causally reduce the risk of developing multiple sclerosis (MS). This Mendelian randomization study found no significant genetic evidence linking higher PA levels to a lower likelihood of MS.
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.
Related Concept Videos
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
01:19Multiple Sclerosis l: Introduction