Potential Therapeutic Targets of PANoptosis for Myocardial Infarction: A Summary-Data-Based Mendelian Randomization Study Integrating eQTL, mQTL, and Multi-GWAS Data

Acute myocardial infarction (MI), a critical and dangerous manifestation of coronary heart disease resulting from arterial or bypass graft thrombosis, rapidly induces myocardial ischemia and hypoxia, and culminates in cardiac failure [1]. PANoptosis, an inflammasome-dependent, inflammatory form of programmed cell death [2], involves a complex molecular network in which pyroptosis, apoptosis, and necroptosis mediate apoptotic programs in an interconnected manner. However, the causal relationships and regulatory mechanisms linking MI and PANoptosis have not been clarified. In addition, DNA methylation regulates PANoptosis pathways, thereby mediating changes in cardiac diseases [3]. Genome-wide association studies (GWASs) and summary-data-based Mendelian randomization (SMR) are novel methods for identifying potential causal targets by integrating expression quantitative trait loci (eQTL) and methylation quantitative trait loci (mQTL) [4]. GWAS data for MI have been integrated with protein quantitative trait loci (pQTL) data for plasma proteins to obtain therapeutic plasma protein targets [5]. Fernandez-Sanles et al.