Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
Author(s)
Type
Journal Article
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 ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/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.
Date Issued
2016-09-12
Date Acceptance
2016-08-02
Citation
Nature Genetics, 2016, 48, pp.1151-1161
ISSN
1546-1718
Publisher
Nature Publishing Group
Start Page
1151
End Page
1161
Journal / Book Title
Nature Genetics
Volume
48
Sponsor
British Heart Foundation
Home Office
Medical Research Council (MRC)
Wellcome Trust
Medical Research Council (MRC)
National Institute for Health Research
Action on Hearing Loss
Medical Research Council (MRC)
Grant Number
SP/04/02
PG0484
G0700931
084723/Z/08/Z
G0601966
NF-SI-0611-10136
G51_Chambers
MR/L01341X/1
Subjects
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
Developmental Biology
11 Medical And Health Sciences
06 Biological Sciences
Publication Status
Published