Abstract 4336880: Integrative Genomic and Transcriptomic Analysis of Hypertension in a Taiwanese Population

Abstract

Background: Hypertension is a leading risk factor for cardiovascular disease and is highly prevalent in Asian populations. However, most genome-wide association studies (GWASs) and transcriptome-wide association studies (TWASs) have primarily focused on individuals of European ancestry, limiting generalizability to other ethnic groups. Hypothesis: We hypothesized that integrating GWAS, TWAS, and expression quantitative trait locus (eQTL) analyses in a large Taiwanese cohort would uncover novel hypertension-associated genetic loci and gene expression profiles relevant to Asian populations. Methods: We performed the first combined GWAS, TWAS, and eQTL analysis of hypertension using data from the Taiwan Biobank, including 10,739 hypertensive patients and 49,668 normotensive controls, with 4,512,191 genome-wide single nucleotide polymorphisms (SNPs). GWAS identified susceptibility loci, TWAS assessed gene-level associations, and eQTL analysis linked significant variants to gene expression changes in whole blood. Results: We identified 14 genetic loci significantly associated with hypertension, including one novel locus at 5p13.1. eQTL analysis revealed that this locus was significantly associated with DAB2 expression in whole blood. TWAS identified 55 hypertension-associated genes, 20 (36%) of which overlapped with GWAS loci. Notably, several genes outside of GWAS-identified loci—such as FBXL15 , KCNIP2 , and CRIP3 —were highly significant in TWAS and are implicated in vascular function and blood pressure regulation. Conclusions: This integrative genomic and transcriptomic study highlights novel genetic contributors to hypertension in an East Asian population. The findings improve our understanding of hypertension biology and may inform future precision medicine approaches for risk prediction and therapeutic development in diverse populations.