Blood pressure and hypertension are associated with 7 loci in the Japanese population

Circulation. 2010 Jun 1;121(21):2302-9. doi: 10.1161/CIRCULATIONAHA.109.904664. Epub 2010 May 17.

Abstract

Background: Two consortium-based genome-wide association studies have recently identified robust and significant associations of common variants with systolic and diastolic blood pressures in populations of European descent, warranting further investigation in populations of non-European descent.

Methods and results: We examined the associations at 27 loci reported by the genome-wide association studies on Europeans in a screening panel of Japanese subjects (n=1526) and chose 11 loci showing association signals (1-tailed test in the screening, P<0.3) for an extensive replication study with a follow-up panel of 3 Japanese general-population cohorts (n < or =24 300). Significant associations were replicated for 7 loci-CASZ1, MTHFR, ITGA9, FGF5, CYP17A1-CNNM2, ATP2B1, and CSK-ULK3-with any or all of these 3 traits: systolic blood pressure (P=1.4x10(-14) to 0.05), diastolic blood pressure (P=1.9x10(-12) to 0.05), and hypertension (P=2.0x10(-14) to 0.006; odds ratio, 1.10 to 1.29). The strongest association was observed for FGF5. In the whole study panel, the variance (R(2)) for blood pressure explained by the 7 single-nucleotide polymorphism loci was calculated to be R(2)=0.003 for male and 0.006 for female participants. Stratified analysis implied the potential presence of a gene-age-sex interaction, although it did not reach a conclusive level of statistical significance after adjustment for multiple testing.

Conclusions: We have confirmed 7 loci associated with blood pressure and/or hypertension in the Japanese. These loci can guide fine-mapping efforts to pinpoint causal variants and causal genes with the integration of multiethnic results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Asian Continental Ancestry Group / ethnology
  • Asian Continental Ancestry Group / genetics*
  • Blood Pressure / genetics*
  • Cross-Sectional Studies
  • DNA-Binding Proteins / genetics
  • Female
  • Fibroblast Growth Factor 5 / genetics
  • Genetic Loci / genetics*
  • Humans
  • Hypertension / genetics*
  • Integrins / genetics
  • Japan
  • Male
  • Middle Aged
  • Plasma Membrane Calcium-Transporting ATPases / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Protein-Serine-Threonine Kinases / genetics
  • Steroid 17-alpha-Hydroxylase / genetics
  • Transcription Factors / genetics
  • Young Adult

Substances

  • ATP2B1 protein, human
  • CASZ1 protein, human
  • DNA-Binding Proteins
  • FGF5 protein, human
  • Integrins
  • Transcription Factors
  • integrin alpha 9, human
  • Fibroblast Growth Factor 5
  • CYP17A1 protein, human
  • Steroid 17-alpha-Hydroxylase
  • Protein-Serine-Threonine Kinases
  • ULK3 protein, human
  • Plasma Membrane Calcium-Transporting ATPases