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Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Original publication

DOI

10.1038/ng.361

Type

Journal article

Journal

Nature genetics

Publication Date

06/2009

Volume

41

Pages

666 - 676

Addresses

Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. cnewtoncheh@chgr.mgh.harvard.edu

Keywords

Wellcome Trust Case Control Consortium, Humans, Cardiovascular Diseases, Cytochrome P-450 CYP1A2, Steroid 17-alpha-Hydroxylase, Methylenetetrahydrofolate Reductase (NADPH2), Proteins, DNA-Binding Proteins, Chromosome Mapping, Blood Pressure, Diastole, Systole, Polymorphism, Single Nucleotide, Open Reading Frames, European Continental Ancestry Group, India, Europe, Fibroblast Growth Factor 5, Phospholipase C delta, Genetic Variation, Genome-Wide Association Study