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Whole -genome survival analysis of 144 286 people from the UK Biobank identifies novel loci associated with blood pressure

Lookup NU author(s): Dr Rebecca Darlay, Professor Bernard Keavney, Professor Heather Cordell

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2024 The Author(s). This study utilized UK Biobank data from 144 286 participants and employed whole-genome sequencing (WGS) data and time-to-event data over a 12-year follow-up period to identify susceptibility in genetic variants associated with hypertension. Following genotype quality control, 6 319 822 single nucleotide polymorphisms underwent analysis, revealing 31 significant variant-level associations. Among these, 29 were novel - 15 in Fibrillin-2 (FBN2) and 4 in Junctophilin-2 (JPH2). Mendelian randomization utilizing two identified variants (rs17677724 and rs1014754) suggested that a genetically induced decrease in heart FBN2 expression and an increase in adrenal gland JPH2 expression were causally linked to hypertension. Phenome-wide association (PheWAS) analysis using the FinnGen dataset confirmed positive associations of rs17677724 and rs1014754 with hypertension, assessed across 2727 traits in 377 277 individuals. Lastly, rs1014754 positively associated with kallistatin, whereas rs17677724 negatively associated with renin in the Fenland study, suggesting a counterregulatory response to high blood pressure. This study, employing WGS data, identified novel genetic loci and potential therapeutic targets for hypertension.


Publication metadata

Author(s): Saluja S, Darlay R, Lennon R, Keavney BD, Cordell HJ

Publication type: Article

Publication status: Published

Journal: Journal of Hypertension

Year: 2024

Volume: 42

Issue: 9

Pages: 1647-1652

Print publication date: 01/09/2024

Online publication date: 10/07/2024

Acceptance date: 11/06/2024

Date deposited: 05/08/2024

ISSN (print): 0263-6352

ISSN (electronic): 1473-5598

Publisher: Lippincott Williams and Wilkins

URL: https://doi.org/10.1097/HJH.0000000000003801

DOI: 10.1097/HJH.0000000000003801

Data Access Statement: The raw genetic and phenotypic data utilized in this study are accessible through the UK Biobank (http://www.ukbiobank.ac.uk/).

PubMed id: 39011893


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Funding

Funder referenceFunder name
203914/Z/16/ZWellcome Trust
219424/Z/19/Z
227417/Z/23/Z
CH/13/2/30154
British Heart Foundation

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