A new insight of hypertrophic cardiomyopathy: integrated analysis of differentially expressed genes, expression quantitative trait loci, and mendelian randomization

Hypertrophic cardiomyopathy (HCM) has a genetic basis, with pathogenic variants identified in the majority of familial cases and unclear mechanism. This study aimed to identify the genetic contributors underlying HCM pathogenesis and to identify novel genetic targets of HCM via integrated analysis of microarray datasets. Three independent HCM datasets were used for comprehensive analysis by using R software. Differentially expressed genes (DEGs) between HCM and control, expression quantitative trait loci (eQTL) analysis, and Two-Sample Mendelian Randomization (TSMR) analyses were performed to identify the novel genes. CIBERSORT was utilized for immune cell infiltration analysis. Finally, the identified genes were verified, and their targeted drugs were explored. TSMR analysis revealed that four significantly HCM co-expressed genes, TNNT1 , KCNK17 , GADD45B , and CXCL6 , were enriched in essential biological processes and pathways, including macrophage activation and neural system regulation. TNNT1 and CXCL6 genes were validated as the novel genes, enhancing the reliability of our findings. The candidate compounds with predicted binding affinity (Atorvastatin, Zearalenone, Cotinine, and S-1,2-Dichlorovinyl-N-acetylcysteine) were predicted and molecular docking was performed to evaluate the binding ability of the drug to the protein. This study reveals a new molecular insight in the pathogenesis of HCM, highlighting TNNT1 and CXCL6 as candidate targets in specific molecular pathways for the interference of HCM.