Yu Qing, Wei Wei, Yuan Ying
Department of Acupuncture and Neurology, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China.
Department of Geriatric, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China.
Brain Behav. 2025 Aug;15(8):e70787. doi: 10.1002/brb3.70787.
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.
尽管先前的观察性研究表明缺血性中风（IS）与阻塞性睡眠呼吸暂停（OSA）之间可能存在关联，但两者之间的因果关系仍不清楚。本研究的目的是通过孟德尔随机化（MR）方法评估IS（包括大动脉中风（LAS）、心源性栓塞性中风（CES）、小血管中风（SVS））与OSA之间的因果关联。
为避免不同遗传背景人群之间的异质性导致的偏差，本研究仅选择与欧洲人群相关的数据库进行分析。我们采用两样本孟德尔随机化分析来检验IS（n = 440,328）、LAS（n = 410,484）、CES（n = 413,304）、SVS（n = 198,048）和OSA（n = 451,618）之间的因果关系。采用逆方差加权（IVW）方法作为主要分析方法来评估因果关系，并使用留一法、MR-Egger截距检验、MR-PRESSO全局检验和异质性检验进行敏感性分析。
MR分析结果显示，基因预测的CES与OSA风险较高相关（IVW：OR = 1.07，95%CI [1.02, 1.13]，p = 0.004），但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）和SVS（IVW：OR = 0.99，95%CI [0.92, 1.08]，p = 0.893）与OSA的发病率没有直接因果关联。上述结果未检测到异质性水平（p > 0.05），敏感性分析也表明没有显著异质性。
尽管OSA与IS、LAS或SVS之间没有直接的因果联系，但本研究表明CES是OSA的一个风险因素，并且CES和OSA在基因水平上呈正相关。
