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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.

Original publication

DOI

10.1016/j.ajhg.2013.12.016

Type

Journal article

Journal

American journal of human genetics

Publication Date

03/2014

Volume

94

Pages

349 - 360

Addresses

Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands; Department of Medical Genetics, Biomedical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.

Keywords

Humans, Risk Factors, Computational Biology, Genetics, Population, Blood Pressure, Diastole, Systole, Genotype, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quality Control, European Continental Ancestry Group, Europe, Genome-Wide Association Study, Genetic Loci, Arterial Pressure