Document Type

Article

Publication Date

12-1-2022

Publication Title

Biochem Biophys Rep

Keywords

JMG

JAX Source

Biochem Biophys Rep. 2022;32:101387

Volume

32

First Page

101387

ISSN

2405-5808

PMID

36438602

DOI

https://doi.org/10.1016/j.bbrep.2022.101387

Grant

This study was supported by Natural Science Basic Research Plan in Shaanxi Province of China (No.2022JM-440); National Natural Science Foundation of China (No. 31371298; 81301151); Xi’an Science and Technology Planning Project (No.21YXYJ0039)

Abstract

Hypertension is a leading risk factor of cardiovascular disease and mortality in the population worldwide. Recently, hundreds of genomic loci were reported for hypertension by GWAS, however, the most SNPs are located in intergenic regions of genome, where a functional cause is difficult to determine. In the current study, a TWAS of hypertension was conducted using 452,264 individuals including 84,640 patients. KEGG and GO enrichment analyses were performed for the hypertension-related genes identified via TWAS. PPI network analysis based on the STRING database was also performed to detect TWAS-identified genes in hypertension. We have identified 18,420 genes from the GWAS summary data, and of those 1010 non-overlapping genes expression were significantly associated with hypertension after FDR correction (PFDR <0.05) in four tissues (left heart ventricle, aorta, whole blood, and peripheral blood). The KEGG and GO terms were mostly related to autoimmune mechanisms, and the autoimmune-related pathways have also been enriched using GO analysis for PPI genes. We further performed Mendelian randomization analysis, and the results supported a significant association between autoimmunity and hypertension. Moreover, 15 novel hypertension-susceptible genes were identified in all tissues, and five of the genes (RBM6, HLA-DRB5, UHRF1BP1, LYZ, and TMEM116) were associated with autoimmune system, which provide further evidence supporting an autoimmune mechanism in hypertension. In summary, our study supports that an autoimmune mechanism plays an important role in the development of hypertension, and these findings will provide new biological insights that will assist in deciphering the molecular etiology of hypertension.

Comments

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/).

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