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

Sihui Huang; Jie Wang; Nannan Liu; Ping Li; Sha Wu; Luming Qi; Lina Xia

doi:10.3389/fgene.2023.1114174

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

Front Genet. 2023 Feb 10:14:1114174. doi: 10.3389/fgene.2023.1114174. eCollection 2023.

Authors

Sihui Huang^{1

2

3}, Jie Wang^{1

2}, Nannan Liu^{1

2}, Ping Li^{1

2}, Sha Wu^{1

2}, Luming Qi^{1

2}, Lina Xia^{1

2}

Affiliations

¹ College of Health and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
² Key Laboratory of Traditional Chinese Medicine Regimen and Health Industry Development, State Administration of TCM, Chengdu, China.
³ Leshan Vocational and Technical College, Leshan, China.

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.

Keywords: SMR; TWAS; UTMOST; hypertension; post-gwas.

Grants and funding

This work is supported by the National Natural Science Foundation-Study on the mechanism of preventing and treating salt-sensitive hypertensive vasculopathy through adjusting intestinal micro-ecology with low salt and activating blood circulation method based on the theory of “salt restrict blood” from Neijing. (No. 8197152161).