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Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.
Nat. Genet. 48, 1151-1161 (2016)
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 similar to 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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Genome-wide Association; Gene-centric Array; Cardiovascular-disease; Aging Research; Plasma-levels; Risk-factors; Loci; Charge; Heart; Identification
Language
german
Publication Year
2016
HGF-reported in Year
2016
ISSN (print) / ISBN
1061-4036
e-ISSN
1546-1718
Journal
Nature Genetics
Quellenangaben
Volume: 48,
Issue: 10,
Pages: 1151-1161
Publisher
Nature Publishing Group
Publishing Place
New York, NY
Reviewing status
Peer reviewed
Institute(s)
Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
Institute of Epidemiology (EPI)
POF-Topic(s)
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
90000 - German Center for Diabetes Research
30202 - Environmental Health
90000 - German Center for Diabetes Research
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-504100-001
G-504000-002
G-504000-006
G-504091-002
G-504091-004
G-501900-401
G-504000-002
G-504000-006
G-504091-002
G-504091-004
G-501900-401
DOI
10.1038/ng.3654
WOS ID
WOS:000384391600010
Erfassungsdatum
2016-10-24