A cross-tissue transcriptome association study identifies key genes in essential hypertension.

Area of Science:

• Genetics
• Cardiovascular Disease Research
• Bioinformatics

Background:

• Genome-wide association studies (GWAS) have identified numerous blood pressure loci, but explain only a small fraction of heritability.
• Transcriptome-wide association studies (TWAS) offer a powerful approach to identify genes influencing complex traits by integrating genetic and gene expression data.

Purpose of the Study:

• To identify novel genes associated with essential hypertension using TWAS by combining large-scale GWAS summary statistics with GTEx eQTL data.
• To validate candidate genes using multiple TWAS methods and statistical validation.

Main Methods:

• Utilized GWAS summary data (N=450,584) for essential hypertension in European samples.
• Performed TWAS using FUMA, FUSION, and UTMOST software, integrating with GTEx v8 eQTL data.
• Validated findings using the SMR (Simple Mạnh Regression) method.

Main Results:

• FUMA identified 346 significant genes, FUSION identified 461, and UTMOST identified 34 genes associated with hypertension.
• Five genes were common across all TWAS methods.
• SMR validation highlighted three key genes: ENPEP, USP38, and KCNK3.

Conclusions:

• TWAS provides a robust framework for discovering genes implicated in essential hypertension, complementing traditional GWAS.
• ENPEP and KCNK3 have established roles in blood pressure regulation, while USP38 requires further investigation for its role in blood pressure.
• This study refines the genetic architecture of hypertension and identifies potential therapeutic targets.