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Lookup NU author(s): Dr Rebecca Darlay, Professor Bernard Keavney, Professor Heather Cordell
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 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.
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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