New blood pressure associated loci identified in meta-analyses of 475,000 individuals

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Title: New blood pressure associated loci identified in meta-analyses of 475,000 individuals
Author(s): Kraja, AT
Evangelou, E
Tzoulaki, I
Zhang, W
Gao, H
Chambers, J
Jarvelin, MR
Kooner, J
Poulter, N
Sever, P
Vergnaud, AC
Elliott, P
CHARGE EXOME BP, CHD Exome+, Exome BP, GoT2D:T2DGenes Consortia
The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group†
Item Type: Journal Article
Abstract: Background—Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association. Methods and Results—Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ≈475 000), and the other in the subset of individuals of European descent (≈423 000). Twenty-one SNVs were genome-wide significant (P<5×10−8) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant. Conclusions—We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
Publication Date: 13-Oct-2017
Date of Acceptance: 17-Aug-2017
URI: http://hdl.handle.net/10044/1/50614
DOI: https://dx.doi.org/10.1161/CIRCGENETICS.117.001778
ISSN: 1942-325X
Publisher: American Heart Association
Journal / Book Title: Circulation: Cardiovascular Genetics
Volume: 10
Issue: 5
Copyright Statement: © 2017 American Heart Association, Inc.
Sponsor/Funder: Medical Research Council (MRC)
Wellcome Trust
Medical Research Council (MRC)
National Institute for Health Research
British Heart Foundation
National Institute for Health Research
National Institute for Health Research
Medical Research Council (MRC)
Medical Research Council (MRC)
National Institute for Health Research
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: G0700931
084723/Z/08/Z
G0601966
NF-SI-0611-10136
SP/13/2/30111
NF-SI-0513-10059
NF-SI-0513-10059
MR/L01632X/1
MR/L01341X/1
RTJ6219303-1
MR/L01632X/1
RDF03
Keywords: Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Genetics & Heredity
Cardiovascular System & Cardiology
blood pressure
exome
genetics
genotype
sample size
GENOME-WIDE ASSOCIATION
COMPARATIVE RISK-ASSESSMENT
FUNCTIONAL VARIATION
SYSTEMATIC ANALYSIS
SCAVENGER RECEPTOR
FAT DISTRIBUTION
GLOBAL BURDEN
VARIANTS
DISEASE
COMMON
blood pressure
exome
genetics
genotype
sample size
Antiporters
Blood Pressure
Cell Adhesion Molecules, Neuronal
Databases, Factual
Genetic Loci
Genome-Wide Association Study
Genotype
Humans
Microfilament Proteins
Phenotype
Polymorphism, Single Nucleotide
Receptors, Lymphocyte Homing
Understanding Society Scientific Group
CHARGE EXOME BP, CHD Exome+, Exome BP, GoT2D:T2DGenes Consortia, The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group†
Humans
Microfilament Proteins
Antiporters
Cell Adhesion Molecules, Neuronal
Receptors, Lymphocyte Homing
Blood Pressure
Genotype
Phenotype
Polymorphism, Single Nucleotide
Databases, Factual
Genome-Wide Association Study
Genetic Loci
0604 Genetics
1102 Cardiovascular Medicine And Haematology
Cardiovascular System & Hematology
Publication Status: Published
Article Number: e001778
Appears in Collections:National Heart and Lung Institute
Department of Medicine
Faculty of Medicine
Epidemiology, Public Health and Primary Care



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