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

Abstract

Genome-wide association study (GWAS) have identified over 1,000 loci associated with blood pressure. However, these loci only explain 6% of heritability. Transcriptome-wide association studies (TWAS) combine GWAS summary data with expression quantitative trait loci (eQTL) to provide a better approach to finding genes associated with complex traits. GWAS summary data (N = 450,584) for essential hypertension originating from European samples were subjected to Post-GWAS analysis using FUMA software and then combined with eQTL data from Genotype-Tissues Expression Project (GTEx) v8 for TWAS analysis using UTMOST, FUSION software, and then validated the results with SMR. FUMA identified 346 significant genes associated with hypertension, FUSION identified 461, and UTMOST cross-tissue analysis identified 34, of which 5 were common. SMR validation identified 3 key genes: ENPEP, USP38, and KCNK3. In previous GWAS studies on blood pressure regulation, the association of ENPEP and KCNK3 with hypertension has been established, and the association between USP38 and blood pressure regulation still needs further validation.