Hui Lu1, Peng-Fei Wu2,3, Rui-Zhuo Li4, Wan Zhang3,5, Guo-Xiang Huang6. 1. Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China. erjihuixin@163.com. 2. Hunan Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China. 3. Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. 4. Department of Ultrasonography, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China. 5. Biology Department, College of Arts and Sciences, Boston University, Boston, MA, USA. 6. Department of Neurology, Affiliated Hospital of Nantong University, Nantong, China.
Abstract
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.
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.
Authors: Curtis W Noonan; Dhelia M Williamson; Judy P Henry; Robert Indian; Sharon G Lynch; John S Neuberger; Randolph Schiffer; Janine Trottier; Laurie Wagner; Ruth Ann Marrie Journal: Prev Chronic Dis Date: 2009-12-15 Impact factor: 2.830