Molecular Mechanisms and Therapeutic Targets in Hypertrophic Cardiomyopathy Insights from Genome-Wide Association Studies and CRISPR-Based Gene Editing Models in Induced Pluripotent Stem Cell-Derived Cardiomyocytes

This study explores the molecular mechanisms and emerging therapeutic targets in hypertrophic cardiomyopathy (HCM) by integrating findings from genome-wide association studies (GWAS) with advanced CRISPR-based gene editing models in induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). The research focuses on identifying genetic variants and molecular pathways that contribute to sarcomeric dysfunction, myocardial hypertrophy, fibrosis, and arrhythmogenesis in HCM. GWAS analyses help uncover both common and rare genetic determinants associated with disease susceptibility and phenotypic variability. CRISPR gene editing is used to model specific pathogenic mutations in iPSC-derived cardiomyocytes, allowing detailed investigation of cellular, electrophysiological, and structural abnormalities. By combining genetic discovery with functional cellular modeling, the study aims to improve understanding of HCM pathophysiology and identify novel precision-based therapeutic targets, potentially supporting the development of gene-modifying and disease-specific treatment strategies.