Whole Genome Sequencing in Premature Coronary Artery Disease in South Asians: A Pilot Case Control Study

Abstract

Background/ObjectivesCoronary artery disease (CAD) remains the leading cause of mortality worldwide, with South Asia bearing a disproportionately high and rising burden, particularly at younger ages. This pilot study aimed to investigate genetic variants associated with premature coronary artery disease (PCAD) using whole genome sequencing (WGS). MethodsWGS was conducted on 12 people (5 PCAD cases, 7 matched controls) to assess feasibility and methodology for future large-scale research. High-quality genomic DNA was sequenced at a minimum read depth of 10x with a quality threshold of Q30. Variant calling with stringent quality control identified single nucleotide polymorphisms (SNPs), followed by annotation against gnomAD for allele frequencies and ClinVar for pathogenicity. Protein-coding variants were filtered, and candidate genes were prioritized for comparative analysis between cases and controls. ResultsAn average of over 8.8 million SNPs per individual was identified, with comparable overall variant distributions between cases and controls. Initial analyses revealed 120 SNPs exclusively present in PCAD cases. All protein-coding variants were rare (allele frequency View larger version (33K): org.highwire.dtl.DTLVardef@1429c57org.highwire.dtl.DTLVardef@264dd8org.highwire.dtl.DTLVardef@c0c6f6org.highwire.dtl.DTLVardef@46752d_HPS_FORMAT_FIGEXP M_FIG C_FIG