Sleep Duration and Stroke: Prospective Cohort Study and Mendelian Randomization Analysis.

Abstract

Studies of sleep duration in relation to specific types of stroke are scarce. Moreover, the results are inconclusive and causality remains unclear. Our objective was to investigate whether sleep duration is associated with risk of stroke and its types using observational and Mendelian randomization designs. The prospective study included 79 881 women and men (45-79 years of age) who were followed up for incident stroke or death over a mean follow-up of 14.6 years (1 164 646 person-years) through linkage to Swedish Registers. For the Mendelian randomization study, single-nucleotide polymorphisms associated with sleep duration were identified from a genome-wide association study. Summarized data for genetic associations with stroke were obtained from publicly available data of the MEGASTROKE and the International Stroke Genetics Consortia. Compared with normal sleep duration, long sleep (≥9 hours per day) was associated with increased risk of total and ischemic stroke (hazard ratios [95% CI], 1.12 [1.03-1.22] and 1.14 [1.03-1.24], respectively), whereas short sleep (<7 h/d) was linked to higher risk of intracerebral hemorrhage (hazard ratio [95% CI], 1.21 [1.03-1.41]). The 2-sample Mendelian randomization analysis supported no causal association of short or long sleep duration with ischemic stroke as a whole. In a prospective study, long sleep duration was associated with increased risk of total and ischemic stroke, whereas short sleep was linked to increased risk of intracerebral hemorrhage. However, the Mendelian randomization analysis did not show a significant detrimental effect of short or long sleep duration on the risk of total stroke or stroke types.