Detection of High-Risk Pathogenic Alleles for Young-Onset Myocardial Infarction in a Malaysian Cohort: A Pilot Study

Abstract

INTRODUCTION: Identifying pathogenic genetic variants associated with young-onset myocardial infarction (YOMI) may facilitate early risk stratification and enable timely preventive intervention. This pilot study aimed to compare the genetic profiles of patients with YOMI with healthy controls to identify high-risk genetic variants and evaluate the utility of polygenic risk scores (PRS) in differentiating genetic susceptibility between the two groups. MATERIALS AND METHODS: Genomic DNA was extracted from patients  with YOMI (n=30; mean age = 37.47 ± 3.29 years) and healthy controls (n=12; mean age =34.67 ± 2.71 years). Samples were genotyped using the Asian Screening Array (Infinium®, Illumina). Genetic variants associated with cardiovascular risk were identified through annotation against the Genome-Wide Association Studies (GWAS) database. Polygenic risk scores were calculated and compared between the two groups. RESULTS: Thirty-seven single nucleotide polymorphisms (SNPs) with odds ratios greater than 2 were identified, including variants associated with coronary heart disease, venous thromboembolism, and atrial fibrillation. The rs13082914 variant in KCNAB1 showed a strong association with young-onset myocardial infarction (OR=8.63; P<0.05). Polygenic risk score analysis revealed higher risk loads in YOMI patients for Brugada syndrome, myocardial infarction in CAD, peripheral artery disease, and non-BMPR2 pulmonary arterial hypertension. CONCLUSION: This pilot study demonstrated the potential value of genetic screening to identify individuals at risk of developing YOMI. However, larger prospective studies are required to validate these findings and to determine their clinical utility in risk prediction and preventive cardiovascular care.