Mendelian randomization and single-cell analysis reveal relationships between sleep disorders and myocardial infarction

Abstract

BackgroundMyocardial infarction (MI) and sleep apnoea are common diseases, and epidemiologic evidence suggests that the two are related. Methods Our research relied on genome-wide association summary statistics (GWAS) pertaining to patients diagnosed with sleep apnoea, snoring, insomnia, or narcolepsy, as well as individuals diagnosed with MI. Using a bidirectional Mendelian randomization (MR) approach, we investigated the relationships between MI and sleep apnoea, snoring, insomnia and narcolepsy. In addition, colocalization analysis was used to identify genes whose increased expression may contribute to sleep disorders. Subsequently, we illustrated that the upregulation of these genes serves as a negative prognostic factor for MI through the application of summary-data-based MR (SMR). Furthermore, we analysedsingle-cell data obtained from individuals with MI to elucidate the subcellular localization of these genes and assess the enriched pathways. ResultsBidirectional MR analysis suggested no causal association between sleep apnoea and MI. Snoring, insomnia, and narcolepsy are risk factors for MI. The genes associated with snoring, insomnia, and narcolepsy were all colocalized with eQTLs. SMR demonstrated that these genes are risk factors for MI. Single-cell analysis revealed that these genes were predominantly localized to cardiac endothelial cells and enriched in the Rap1 pathway. Conclusion Our study revealedthat snoring, insomnia, and narcolepsy are risk factors for MI. The primary mechanism could involve sleep disorders inducing alterations in the expression abundance of LINC02210, LRRC37A, LRRC37A2, KANSL1-AS1, and DND1P1, thereby increasing the risk of MI via the Rap1 pathway.