Genomics of hypertension: the road to precision medicine

Padmanabhan, S. and Dominiczak, A. F. (2021) Genomics of hypertension: the road to precision medicine. Nature Reviews Cardiology, 18(4), pp. 235-250. (doi: 10.1038/s41569-020-00466-4) (PMID:33219353)

Abstract

The known genetic architecture of blood pressure now comprises >30 genes, with rare variants resulting in monogenic forms of hypertension or hypotension and >1,477 common single-nucleotide polymorphisms (SNPs) being associated with the blood pressure phenotype. Monogenic blood pressure syndromes predominantly involve the renin–angiotensin–aldosterone system and the adrenal glucocorticoid pathway, with a smaller fraction caused by neuroendocrine tumours of the sympathetic and parasympathetic nervous systems. The SNPs identified in genome-wide association studies (GWAS) as being associated with the blood pressure phenotype explain only approximately 27% of the 30–50% estimated heritability of blood pressure, and the effect of each SNP on the blood pressure phenotype is small. A paucity of SNPs from GWAS are mapped to known genes causing monogenic blood pressure syndromes. For example, a GWAS signal mapped to the gene encoding uromodulin has been shown to affect blood pressure by influencing sodium homeostasis, and the effects of another GWAS signal were mediated by endothelin. However, the majority of blood pressure-associated SNPs show pleiotropic associations. Unravelling these associations can potentially help us to understand the underlying biological pathways. In this Review, we appraise the current knowledge of blood pressure genomics, explore the causal pathways for hypertension identified in Mendelian randomization studies and highlight the opportunities for drug repurposing and pharmacogenomics for the treatment of hypertension.

• Item Type: Articles
• Additional Information: S.P. is funded by the Medical Research Council (MR/M016560/1), the British Heart Foundation (PG/12/85/29925, CS/16/1/31878, RE/18/6/34217), Health Data Research UK and Chief Scientist Office, Scotland. A.F.D. acknowledges funding from UK Research and Innovation Strength in Places Fund (SIPF) 35049.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Padmanabhan, Professor Sandosh and Dominiczak, Professor Anna
• Authors: Padmanabhan, S., and Dominiczak, A. F.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Nature Reviews Cardiology
• Publisher: Nature Research
• ISSN: 1759-5002
• ISSN (Online): 1759-5010
• Published Online: 20 November 2020
• Copyright Holders: Copyright © 2020 Springer Nature Limited
• First Published: First published in Nature Reviews Cardiology 18(4): 235-250
• Publisher Policy: Reproduced in accordance with the publisher copyright policy