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

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.

Sleep Duration and Stroke: A Mendelian Randomization Study.

Study Objectives: To clarify the effects of sleep duration on stroke and stroke subtypes, we adopted a Mendelian randomization (MR) approach to evaluate their causal relationship. Methods: A genome-wide association study including 446,118 participants from UK biobank was used to identify instruments for short sleep, long sleep and sleep duration. Summary-level data for all stroke, ischemic stroke, intracerebral hemorrhage, and their subtypes were obtained from meta-analyses conducted by the MEGASTROKE consortium. MR analyses were performed using the inverse-variance-weighted method, weighted median estimator, MR pleiotropy residual sum and outlier (MR-PRESSO) test, and MR-Egger regression. Sensitivity analyses were further performed using leave-one-out analysis, MR-PRESSO global test and Cochran's Q test to verify the robustness of our findings. Results: By two-sample MR, we didn't find causal associations between sleep duration and risk of stroke. However, in the subgroup analysis, we found weak evidence for short sleep in increasing risk of cardio-embolic stroke (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.11-1.60; P = 0.02) and long sleep in increasing risk of large artery stroke [OR, 1.41; 95% CI, 1.02-1.95; P = 0.04]. But the associations were not significant after Bonferroni correction for multiple comparisons. Conclusions: Our study suggests that sleep duration is not causally associated with risk of stroke and its subtypes.

Detailed Echocardiographic Measurements of Individual Chamber in a Chinese Cohort of Hypoplastic Left Heart Syndrome and Comparison with Normal Fetuses via Z-score Modeling.

Hypoplastic left heart syndrome (HLHS) is a rare, but exceptionally serious, congenital heart defect. We aimed to explore the best-fitted Z-score models for individual chamber dimension and to draw a comparison between fetuses with HLHS and the normal Chinese cohort. We made measurements of 1674 healthy fetuses and 79 fetuses with HLHS, undertaking echocardiography. Normal fetal cardiovascular Z-score formulae were established by curve-fitting with 5 algorithmic functions and weighted regression of absolute residuals. Classic linear models were fitted for left ventricular diameter against gestational age, and log-transformed linear-power models-were statistically better for left ventricular length, diameter of left atrium and ascending aorta. Fetuses with HLHS manifested significantly lower Z-score means (≤3.5) for these 4 parameters and the vast majority (∼90%) lay beyond -2. Overall, cardiovascular Z-score equations were reliably constructed in a larger Chinese cohort, and their application should benefit evaluation and diagnosis of HLHS.