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New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals.

TitleNew Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals.
Publication TypeJournal Article
Year of Publication2017
AuthorsKraja AT, Cook JP, Warren HR, et al.
Secondary AuthorsHowson JMM
Corporate AuthorsUnderstanding Society Scientific Group, CHARGE EXOME BP, CHD Exome+, Exome BP, GoT2D:T2DGenes Consortia, The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group†
JournalCirc Cardiovasc Genet
Volume10
Issue5
Date Published2017 Oct
ISSN1942-3268
KeywordsAntiporters, 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
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 (

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.

DOI10.1161/CIRCGENETICS.117.001778
Alternate JournalCirc Cardiovasc Genet
PubMed ID29030403
PubMed Central IDPMC5776077
Grant ListN01WH44221 / WH / WHI NIH HHS / United States
R01 HL071252 / HL / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
N01WH22110 / WH / WHI NIH HHS / United States
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RC4 AG039029 / AG / NIA NIH HHS / United States
G9521010 / MRC_ / Medical Research Council / United Kingdom
N01WH32100 / WH / WHI NIH HHS / United States
G1001799 / MRC_ / Medical Research Council / United Kingdom
R01 HL103612 / HL / NHLBI NIH HHS / United States
R01 MH063706 / MH / NIMH NIH HHS / United States
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MC_QA137853 / MRC_ / Medical Research Council / United Kingdom
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SP/13/2/30111 / BHF_ / British Heart Foundation / United Kingdom
HHSN268200800007C / HL / NHLBI NIH HHS / United States
G0700931 / MRC_ / Medical Research Council / United Kingdom
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RG/08/014/24067 / BHF_ / British Heart Foundation / United Kingdom
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