Functional Pathway Analysis of Genetic Variants associated with Hypertension: A Comprehensive In Silico Approach

Hypertension is a complex multifactorial disorder with significant genetic components. Genome-wide association studies (GWAS) have identified several genetic variants associated with hypertension. This study aimed to identify biological pathways and molecular mechanisms potentially involved in hypertension pathogenesis through in silico functional analysis of GWAS-identified variants. We conducted a comprehensive pathway analysis of five genes (CHRM3, ATP2B1, CACNB2, MSRA, UMOD and ZNF831) previously associated with hypertension through GWAS. Multiple databases enriched biological processes, cellular components, molecular functions, metabolic pathways, miRNA targets, protein-protein interactions and gene expression signatures. Our analysis revealed significant enrichment in several pathways critical to hypertension pathophysiology. Key biological processes included regulation of smooth muscle contraction (p=2.65×10^-5), vasoconstriction (p=4.53×10^-5) and calcium ion transport (p=5.65×10^-5). Molecular function analysis highlighted calcium ion transmembrane transporter activity (p=3.15×10^-4). Enriched cellular components included basolateral plasma membrane (p=1.97×10^-3) and voltage-gated calcium channel complexes (p=1.94×10^-2). Pathway analysis identified significant associations with sensory processing of sound (p=3.24×10^-4), cardiac conduction (p=1.14×10^-3) and regulation of insulin secretion (p=4.14×10^-4). Our findings provide new insights into the molecular mechanisms underlying hypertension, particularly highlighting the importance of calcium signaling, smooth muscle contraction and vasoconstriction. These results suggest potential therapeutic targets and may contribute to the development of personalized medicine approaches for hypertension management.