Association between Sleep Disorders and risk of stroke: insights from cross-sectional study and Mendelian randomization

Objective: This study aimed to systematically evaluate the causal associations between various sleep disorders (SD) and stroke risk by integrating cross-sectional observational analyses with Mendelian randomization (MR) approaches. Methods: A cross-sectional analysis was performed using data from the National Health and Nutrition Examination Survey (NHANES, 2015–2018), including 7,264 participants, 270 of whom had a history of stroke. Logistic regression models assessed the association between SD and stroke risk. Eight sleep disorders were examined: sleep terrors, sleep-wake schedule disorders, sleepwalking, sleep apnoea, nonorganic sleep disorder, insomnia, trouble falling asleep, and daytime dozing. Genetic instruments (SNPs) for these exposures were retrieved from the IEU Open GWAS database, and two-sample MR analysis was conducted to infer causality. Results: SD showed a strong positive association with stroke in the crude model (OR = 2.62, 95% CI: 1.88–3.64, P < 0.001), which remained significant after adjusting for confounders (OR = 1.83, 95% CI: 1.28–2.63, P = 0.007). MR analysis identified nonorganic sleep disorder (OR = 1.025, P = 0.023) and sleep apnoea (OR = 1.105, P = 0.002) as significant risk factors for stroke. Conversely, sleepwalking showed a negative association (OR = 0.986, P = 0.001). No evidence of horizontal pleiotropy or heterogeneity was detected, and reverse MR showed no causal effect of stroke on SD. Conclusion: Combining observational and genetic evidence, this study supports a causal relationship between certain SD subtypes and stroke risk. Nonorganic sleep disorders and sleep apnoea may increase stroke risk, while sleepwalking may have a protective effect.