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标题：Assessment of causal effects of physical activity on neurodegenerative diseases: A Mendelian randomization study
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作者：Peng-Fei Wu ; Hui Lu ; Xiaoting Zhou 等
期刊名称：Journal of Sport and Health Science
印刷版ISSN：2095-2546
出版年度：2021
卷号：10
期号：4
页码：454-461
DOI：10.1016/j.jshs.2021.01.008
语种：English
出版社：Elsevier
摘要：Highlights • Two-sample Mendelian randomization approaches have been utilized to explore the causal relationship between accelerometer-measured physical activity and 3 common neurodegenerative diseases. • We found no evidence for the casual effect of physical activity on the risk of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis in the European population. • Genetically predicted physical activity was not robustly associated with the risk of 3 common neurodegenerative disorders. Background Physical activity has been hypothesized to play a protective role in neurodegenerative diseases. However, effect estimates previously derived from observational studies were prone to confounding or reverse causation. Methods We performed a two-sample Mendelian randomization (MR) analysis to explore the causal association of accelerometer-measured physical activity with 3 common neurodegenerative diseases: Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). We selected genetic instrumental variants reaching genome-wide significance ( p < 5 × 10 −8) from 2 largest meta-analyses of about 91,100 UK Biobank participants. Summary statistics for AD, PD, and ALS were retrieved from the up-to-date studies in European ancestry led by the international consortia. The random-effect, inverse-variance weighted MR was employed as the primary method, while MR pleiotropy residual sum and outlier (MR-PRESSO), weighted median, and MR-Egger were implemented as sensitivity tests. All statistical analyses were performed using the R programming language (Version 3.6.1; R Foundation for Statistical Computing, Vienna, Austria). Results Primary MR analysis and replication analysis utilized 5 and 8 instrumental variables, which explained 0.2% and 0.4% variance in physical activity, respectively. In each set, one variant at 17q21 was significantly associated with PD, and MR sensitivity analyses indicated them it as an outlier and source of heterogeneity and pleiotropy. Primary results with the removal of outlier variants suggested odds ratios (ORs) of neurodegenerative diseases per unit increase in objectively measured physical activity were 1.52 for AD (95% confidence interval (95%CI): 0.88–2.63, p = 0.13) and 3.35 for PD (95%CI: 1.32–8.48, p = 0.01), while inconsistent results were shown in the replication set for AD (OR = 1.06, 95%CI: 1.01–1.12, p = 0.02) and PD (OR = 0.99, 95%CI: 0.88–0.12, p = 0.97). Similarly, the beneficial effect of physical activity on ALS (OR = 0.51, 95%CI: 0.29–0.91, p = 0.02) was not confirmed in the replication analysis (OR = 0.96, 95%CI: 0.91–1.02, p = 0.22). Conclusion Genetically predicted physical activity was not robustly associated with risk of neurodegenerative disorders. Triangulating evidence across other studies is necessary in order to elucidate whether enhancing physical activity is an effective approach in preventing the onset of AD, PD, or ALS. Graphical Abstract Image, graphical abstract
关键词：Alzheimer's disease;Amyotrophic lateral sclerosis;Genetic epidemiology;Mendelian randomization;Parkinson's disease;Physical activity