Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension



Surendran, Praveen, Drenos, Fotios, Young, Robin, Warren, Helen, Cook, James P, Manning, Alisa K, Grarup, Niels, Sim, Xueling, Barnes, Daniel R, Witkowska, Kate
et al (show 200 more authors) (2016) Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. NATURE GENETICS, 48 (10). pp. 1151-1161.

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Abstract

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.

Item Type: Article
Uncontrolled Keywords: CHARGE-Heart Failure Consortium, EchoGen Consortium, METASTROKE Consortium, GIANT Consortium, EPIC-InterAct Consortium, Lifelines Cohort Study, Wellcome Trust Case Control Consortium, Understanding Society Scientific Group, EPIC-CVD Consortium, CHARGE+ Exome Chip Blood Pressure Consortium, T2D-GENES Consortium, GoT2DGenes Consortium, ExomeBP Consortium, CHD Exome+ Consortium, Humans, Hypertension, Genetic Predisposition to Disease, Blood Pressure, Genotype, Genetic Variation, Genome-Wide Association Study
Depositing User: Symplectic Admin
Date Deposited: 04 Oct 2016 14:53
Last Modified: 19 Jan 2023 07:29
DOI: 10.1038/ng.3654
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3003602