Sleep duration may not have any effect on the risk of stroke: insights from Mendelian randomization and prospective cohort studies

Abstract

Introduction: Due to contentious associations between sleep and stroke risk we performed a meta-analysis of cohort studies and utilized Mendelian randomization (MR). Material and methods: For the meta-analysis we pooled prospective studies and then reviewed the largest genome-wide association studies regarding self-reported or accelerometer-derived sleep duration with stroke [ischemic (IS), cardioembolic (CES), large artery (LAS), small vessel (SVS)]. Inverse variance weighted method (IVW), weighted median (WM)-based method, MR-Egger and MR-Pleiotropy RESidual Sum and Outlier (PRESSO) were performed. To determine the impact of single nucleotide polymorphisms (SNPs) leave-one-out method was applied. Results: Pooled prospective studies demonstrated shorter (<7h) [n=25 studies, I2 = 71. 4, p <0 VSports app下载. 001; risk ratio (RR): 1. 18, 95%CI: 1. 08-1. 30, p <0. 001] and longer (>8h) [n=16 studies, I2 = 53. 6, p <0. 001; RR: 1. 38, 95%CI: 1. 24-1. 53, p <0. 001] sleep increased stroke risk (compared with 7-8h), but were subject to high levels of heterogeneity. In MR, self-reported sleep duration had no significant effect on IS (IVW: beta = -0. 031, p = 0. 747), CES (IVW: beta = -0. 039, p = 0. 849), LAS (IVW: beta = -0. 246, p = 0. 328) and SVS (IVW: beta = -0. 102, p = 0. 667) risk. This was also observed for short and long accelerometer-derived sleep (all p >0. 126). Estimated associations had no significant heterogeneity and MR-PRESSO revealed no outliers. There was low likelihood of pleiotropy (all estimations p >0. 539) and associations were not driven by single SNPs. Conclusions: Meta-analysis revealed shorter and longer sleep increased total stroke risk, but with high heterogeneity. MR analysis showed no causal associations between sleep duration and stroke risk.