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Integrative genomic and transcriptomic analysis of hypertension in a Taiwanese population
Sheng-Nan Chang1, Guan-Wei Lee2, Jien-Jiun Chen3
1Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and Hospital Yun-Ling Branch, Dou-Liu City.
Objectives:
Hypertension is highly prevalent in Asian populations and represents a major cardiovascular risk factor. However, most genome-wide association studies (GWASs) and transcriptome-wide association studies (TWASs) have focused primarily on Caucasian cohorts. This study aimed to identify genetic loci and gene expression signatures associated with hypertension in an Asian population.
Methods:
We analyzed 10 739 hypertensive patients and 49 668 controls from the Taiwan Biobank, testing 4 512 191 genome-wide single nucleotide polymorphisms (SNPs). Integrated GWAS, TWAS, and expression quantitative trait locus (eQTL) analyses were conducted to characterize genetic risk. Additionally, a polygenic risk score (PRS) was constructed using a split-sample design to evaluate genetic risk stratification.
Results:
We identified 14 loci significantly associated with hypertension, including a novel locus at 5p13.1. eQTL analysis linked this locus to DAB2 expression in whole blood. TWAS detected 55 hypertension-associated genes, with 20 (36%) overlapping GWAS loci. Several novel genes outside GWAS loci, including FBXL15, KCNIP2, and CRIP3, were highly significant and implicated in vascular biology and hypertension mechanisms. PRS analysis effectively differentiated hypertension risk, with individuals in the top 10% showing a > 3.5-fold increased risk compared to the bottom 10%.
Conclusions:
Our findings provide new insights into the genetic and transcriptomic landscape of hypertension in Asians. The identification of novel loci and genes advances understanding of disease biology and may guide precision medicine approaches for risk prediction and therapeutic development.
