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

Autor:	Saluja S; Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester.; Division of Medicine and Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust Manchester, Manchester., Darlay R; Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne., Lennon R; Wellcome Centre for Cell-Matrix Research, division of Cell-Matrix biology and regenerative Medicine, School of biological Sciences, Faculty of Biology Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK., Keavney BD; Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester.; Division of Medicine and Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust Manchester, Manchester., Cordell HJ; Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne.
Jazyk:	angličtina
Zdroj:	Journal of hypertension [J Hypertens] 2024 Sep 01; Vol. 42 (9), pp. 1647-1652. Date of Electronic Publication: 2024 Jul 10.
DOI:	10.1097/HJH.0000000000003801
Abstrakt:	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. (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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