Genome-wide association study identifies eight loci associated with blood pressure

Nat Genet. 2009 Jun;41(6):666-76. doi: 10.1038/ng.361. Epub 2009 May 10.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Pressure / genetics*
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / physiopathology
  • Chromosome Mapping
  • Cytochrome P-450 CYP1A2 / genetics
  • DNA-Binding Proteins / genetics
  • Diastole / genetics
  • Europe
  • European Continental Ancestry Group / genetics
  • Fibroblast Growth Factor 5 / genetics
  • Genetic Variation
  • Genome-Wide Association Study*
  • Humans
  • India
  • Intracellular Signaling Peptides and Proteins
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Open Reading Frames / genetics
  • Phospholipase C delta / genetics
  • Polymorphism, Single Nucleotide*
  • Proteins / genetics
  • Steroid 17-alpha-Hydroxylase / genetics
  • Systole / genetics

Substances

  • DNA-Binding Proteins
  • FGF5 protein, human
  • Intracellular Signaling Peptides and Proteins
  • LNK protein, human
  • Proteins
  • ZNF652 protein, human
  • Fibroblast Growth Factor 5
  • CYP1A2 protein, human
  • Cytochrome P-450 CYP1A2
  • CYP17A1 protein, human
  • Steroid 17-alpha-Hydroxylase
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • PLCD3 protein, human
  • Phospholipase C delta

Grant support