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Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci.
Am. J. Hum. Genet. 94, 349-360 (2014)
Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10-7) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Genome-wide Association; Coronary-artery-disease; Human Prefrontal Cortex; Factor-kappa-b; Essential-hypertension; Susceptibility Locus; Candidate Genes; Common Variants; Drug Discovery; Pulse Pressure
ISSN (print) / ISBN
0002-9297
e-ISSN
1537-6605
Quellenangaben
Volume: 94,
Issue: 3,
Pages: 349-360
Publisher
Elsevier
Publishing Place
New York, NY
Non-patent literature
Publications
Reviewing status
Peer reviewed