Functional mutation, splice, distribution, and divergence analysis of impactful genes associated with heart failure and other cardiovascular diseases

Abstract

Abstract Cardiovascular disease (CVD) is caused by a multitude of complex and largely heritable conditions. Identifying key genes and understanding their susceptibility to CVD in the human genome can assist in early diagnosis and personalized treatment of the relevant patients. Heart failure (HF) is among those CVD phenotypes that has a high rate of mortality. In this study, we investigated genes primarily associated with HF and other CVDs. Achieving the goals of this study, we built a cohort of thirty-five consented patients, and sequenced their serum-based samples. We have generated and processed whole genome sequence (WGS) data, and performed functional mutation, splice, variant distribution, and divergence analysis to understand the relationships between each mutation type and its impact. Our variant and prevalence analysis found FLNA, CST3, LGALS3, and HBA1 linked to many enrichment pathways. Functional mutation analysis uncovered ACE, MME, LGALS3, NR3C2, PIK3C2A, CALD1, TEK, and TRPV1 to be notable and potentially significant genes. We discovered intron, 5ʹ Flank, 3ʹ UTR, and 3ʹ Flank mutations to be the most common among HF and other CVD genes. Missense mutations were less common among HF and other CVD genes but had more of a functional impact. We reported HBA1, FADD, NPPC, ADRB2, ADBR1, MYH6, and PLN to be consequential based on our divergence analysis.