Unveiling blood pressure-associated genes in aortic cells through integrative analysis of GWAS and RNA modification-associated variants
- VernacularTitle:Unveiling blood pressure-associated genes in aortic cells through integrative analysis of GWAS and RNA modification-associated variants
- Author:
Huan ZHANG
1
;
Yuxi CHEN
;
Peng XU
;
Dan LIU
;
Naqiong WU
;
Laiyuan WANG
;
Xingbo MO
Author Information
- Publication Type:Journal Article
- Keywords: aortic dissection; blood pressure; genome-wide association study; RNA modification; single-cell
- From: Chronic Diseases and Translational Medicine 2024;10(2):118-129
- CountryChina
- Language:English
- Abstract: Background::Genome-wide association studies (GWAS) have identified more than a thousand loci for blood pressure (BP). Functional genes in these loci are cell-type specific. The aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification-associated single-nucleotide polymorphisms (RNAm-SNPs).Methods::Utilizing large-scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium, we identified associations between RNAm-SNPs and BP. The association between RNAm-SNPs, gene expression, and BP were examined.Results::A total of 355 RNAm-SNPs related to m 6A, m 1A, m 5C, m 7G, and A-to-I modification were associated with BP. The related genes were enriched in the pancreatic secretion pathway and renin secretion pathway. The BP GWAS signals were significantly enriched with m 6A-SNPs, highlighting the potential functional relevance of m 6A in physiological processes influencing BP. Notably, m 6A-SNPs in CYP11B1, PDE3B, HDAC7, ACE, SLC4A7, PDE1A, FRK, MTHFR, NPPA, CACNA1D, and HDAC9 were identified. Differential methylation and differential expression of the BP genes in FTO-overexpression and METTL14-knockdown vascular smooth muscle cells were detected. RNAm-SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection (AD) cases and controls. In scRNA-seq study, we identified ARID5A, HLA-DPB1, HLA-DRA, IRF1, LINC01091, MCL1, MLF1, MLXIPL, NAA16, NADK, RERG, SRM, and USP53 as differential expression genes for AD in aortic cells. Conclusion::The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs, gene expression, and BP. The identified BP-associated genes in aortic cells were associated with AD.
