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Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney

Eales, JM; Jiang, X; Xu, X; Saluja, S; Akbarov, A; Cano-Gamez, E; McNulty, MT; ... Tomaszewski, M; + view all (2021) Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney. Nature Genetics , 53 (5) pp. 630-637. 10.1038/s41588-021-00835-w. Green open access

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Abstract

The kidney is an organ of key relevance to blood pressure (BP) regulation, hypertension and antihypertensive treatment. However, genetically mediated renal mechanisms underlying susceptibility to hypertension remain poorly understood. We integrated genotype, gene expression, alternative splicing and DNA methylation profiles of up to 430 human kidneys to characterize the effects of BP index variants from genome-wide association studies (GWASs) on renal transcriptome and epigenome. We uncovered kidney targets for 479 (58.3%) BP-GWAS variants and paired 49 BP-GWAS kidney genes with 210 licensed drugs. Our colocalization and Mendelian randomization analyses identified 179 unique kidney genes with evidence of putatively causal effects on BP. Through Mendelian randomization, we also uncovered effects of BP on renal outcomes commonly affecting patients with hypertension. Collectively, our studies identified genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to the genetic regulation of BP and inherited susceptibility to hypertension.

Type: Article
Title: Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41588-021-00835-w
Publisher version: https://doi.org/10.1038/s41588-021-00835-w
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10138127
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