Causal Relations Between Obstructive Sleep Apnea and Stroke: A Mendelian Randomization Study

Abstract

Background: Previous studies of obstructive sleep apnea (OSA) in relation to stroke have been noted. However, the exact causality remains to be clearly defined. We aimed to adopt a two-sample Mendelian randomization study to investigate the causal effects of OSA on stroke and its subtypes. Methods: A two-sample Mendelian randomization (MR) analysis was conducted to evaluate the causal effect of OSA on stroke and its subtypes, including, based on publicly genome-wide association studies (GWAS) databases. The inverse variance weighted (IVW) method was used as the main analysis. MR-Egger regression, weighted mode, weighted median, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed methods and were adopted as supplementary analysis to ensure the robustness of the results. Results: Genetically predicted OSA was not related to the risk of stroke (odds ratio (OR), 0.99, 95% CI, 0.81–1.21, p = 0.909), and its subtypes, ischemic stroke (IS) (OR, 1.01, 95% CI, 0.82–1.23, p = 0.927), large vessel stroke (LVS) (OR, 1.05, 95% CI, 0.73–1.51, p = 0.795), cardioembolic stroke (CES) (OR, 1.03, 95% CI, 0.74–1.43, p = 0.855), small vessel stroke (SVS) (OR, 1.13, 95% CI, 0.88– 1.46, p = 0.329), lacunar stroke (LS) (OR, 1.07, 95% CI, 0.74–1.56, p = 0.721) as well as intracerebral hemorrhage (ICH) (OR, 0.37, 95% CI = 0.09, 1.48, p = 0.160) (Wald ratio method). Other supplementary MR methods also confirmed similar results. Conclusion: There may be no direct causal relationship between OSA and stroke or its subtypes.