Kidney omics in hypertension: from statistical associations to biological mechanisms and clinical applications

Tomaszewski, M. et al. (2022) Kidney omics in hypertension: from statistical associations to biological mechanisms and clinical applications. Kidney International, 102(3), pp. 492-505. (doi: 10.1016/j.kint.2022.04.045) (PMID:35690124)

Abstract

Hypertension is a major cardiovascular disease risk factor and contributor to premature death globally. Family-based investigations confirmed a significant heritable component of blood pressure (BP), whereas genome-wide association studies revealed >1000 common and rare genetic variants associated with BP and/or hypertension. The kidney is not only an organ of key relevance to BP regulation and the development of hypertension, but it also acts as the tissue mediator of genetic predisposition to hypertension. The identity of kidney genes, pathways, and related mechanisms underlying the genetic associations with BP has started to emerge through integration of genomics with kidney transcriptomics, epigenomics, and other omics as well as through applications of causal inference, such as Mendelian randomization. Single-cell methods further enabled mapping of BP-associated kidney genes to cell types, and in conjunction with other omics, started to illuminate the biological mechanisms underpinning associations of BP-associated genetic variants and kidney genes. Polygenic risk scores derived from genome-wide association studies and refined on kidney omics hold the promise of enhanced diagnostic prediction, whereas kidney omics-informed drug discovery is likely to contribute new therapeutic opportunities for hypertension and hypertension-mediated kidney damage.

• Item Type: Articles
• Additional Information: This work was supported by British Heart Foundation grants (PG/17/ 35/33001 and PG/19/16/34270) and Kidney Research UK grants (RP_017_20180302 and RP_013_20190305) to MT; and National Institutes of Health (NIH) grants (R01 DK117445-01A1 and R01 MD012765) to NF and APM. APM acknowledges support from Versus Arthritis (grant reference 21754). TJG is funded by European Research Council InflammaTENSION; ERC-CoG-726318 and CVD ERA-CVD (PLAQUEFIGHT; 01KL1808; NCBiR, Poland, and Brain-Gut). SD is funded by NIH grants (R01 HL144943 and R01 HL157583).
• Keywords: Gene expression, ambulatory blood pressure monitoring (ABPM).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Guzik, Professor Tomasz
• Authors: Tomaszewski, M., Morris, A. P., Howson, J. M., Franceschini, N., Eales, J., Xu, X., Dikalov, S., Guzik, T. J., Humphreys, B., Harrap, S., and Charchar, F. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Kidney International
• Publisher: Elsevier
• ISSN: 0085-2538
• ISSN (Online): 1523-1755
• Published Online: 09 June 2022
• Copyright Holders: Copyright © 2022 International Society of Nephrology
• First Published: First published in Kidney International 102(3): 492-505
• Publisher Policy: Reproduced under a Creative Commons License