Genetic association between sleep apnea syndrome and stroke:a mediated Mendelian randomization study

CHEN Wei; WANG Ye

doi:10.12173/j.issn.1004-5511.202412052

Abstract：Objective To explore the causal relationship between sleep apnea syndrome(SAS)and stroke and the possible mediating role of serum metabolites from a genetic perspective based on Mendelian randomization(MR).Methods A two-sample bidirectional MR approach was used to explore the effect of SAS on stroke and its subtypes,and serum metabolites were used as mediators for MR analysis.The inverse-variance weighted(IVW)method was considered as the primary method to evaluate the causal relationship between exposure and outcome.Additionally,sensitivity analyses were performed to evaluate pleiotropy and heterogeneity.Results Two-sample bidirectional MR showed that there was a significant correlation between SAS and lacunar infarction[OR=1.144,95％CI(1.014,1.291),P＜0.05]and large artery atherosclerotic ischemic stroke[OR=1.118,95％CI(1.028,1.371),P＜0.05].Mediating effects showed that SAS increased the risk of largeartery atherosclerotic ischemic stroke by increasing the levels of N6-carbamoylthreonyladenosine[β=0.020,95％CI(0.001,0.038),P=0.035]and 4-hydroxyphenylpyruvic acid[β=0.019,95％CI(0.001,0.036),P=0.037].Conclusion There is a causal relationship in genetics between SAS,lacunar infarction,and large artery atherosclerotic ischemic stroke,and changes in serum metabolite levels may be a potential mechanism underlying the causal relationship between SAS and large artery atherosclerotic ischemic stroke.