A Two-Sample Mendelian Randomization Research Examining the Causal Association Between Ischemic Stroke and Obstructive Sleep Apnea

Although prior observational research has indicated a potential association between ischemic stroke (IS) and obstructive sleep apnea (OSA), it is still unclear how the two conditions are causally related. The purpose of this study is to evaluate the causal association between IS, including large artery stroke (LAS), cardioembolic stroke (CES), small vessel stroke (SVS), and OSA by the Mendelian randomization (MR) approach.

To avoid bias caused by heterogeneity among populations with different genetic backgrounds, this study selected only databases related to the European population for analysis. We adopted a two-sample Mendelian randomization analysis to examine the causal relationship between IS (n = 440,328), LAS (n = 410,484), CES (n = 413,304), SVS (n = 198,048), and OSA (n = 451,618).The inverse variance-weighted (IVW) method was used as the primary analysis method to assess causal relationships, with sensitivity analyses conducted using the leave-one-out method, MR-Egger intercept test, MR-PRESSO global test, and heterogeneity tests.

MR analysis results showed that the gene-predicted CES was associated with a higher risk of OSA (IVW: OR = 1.07, 95% CI [1.02, 1.13], p = 0.004), but IS (IVW: OR = 1.05, 95% CI [0.96, 1.14], p = 0.268), LAS (IVW: OR = 1.01, 95% CI [0.97, 1.04], p = 0.736), and SVS (IVW: OR = 0.99, 95% CI [0.92, 1.08], p = 0.893) were not directly causally associated with the incidence of OSA. No level of heterogeneity was detected in the above results (p > 0.05), and sensitivity analysis also indicated no significant heterogeneity.

Despite there is no direct causative link between OSA and IS, LAS, or SVS, this study indicates that CES is a risk factor for OSA and that CES and OSA are positively correlated at the genetic level.