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

Due to contentious associations between sleep and stroke risk, we performed a meta-analysis of cohort studies and Mendelian randomization (MR) analysis.

For the meta-analysis, we pooled prospective studies and reviewed the largest genome-wide association studies investigating self-reported or accelerometer-derived sleep duration in relation to stroke subtype: ischemic (IS), cardioembolic (CES), large artery (LAS), or small vessel (SVS). The 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), the leave-one-out method was applied.

Pooled prospective studies demonstrated that both shorter (< 7 h) [n = 25 studies, I ² = 71.4, p < 0.001; risk ratio (RR) = 1.18, 95% CI: 1.08-1.30, p < 0.001] and longer (> 8 h) [n = 16 studies, I ² = 53.6, p < 0.001; RR = 1.38, 95% CI: 1.24-1.53, p < 0.001] sleep increased stroke risk (compared with 7-8 h), 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) or 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.

The meta-analysis suggested that shorter and longer sleep may be associated with increased total stroke risk, although these findings were subject to high heterogeneity. In contrast, the MR analysis did not provide evidence of causal associations between sleep duration and stroke risk in this dataset.