Heterogeneous effects of association between blood pressure loci and coronary artery disease in east Asian individuals

Circ J. 2015;79(4):830-8. doi: 10.1253/circj.CJ-14-0841. Epub 2015 Feb 5.

Abstract

Background: A coronary artery disease (CAD) association study of genetic loci previously identified as being associated with blood pressure (BP) was performed in east Asian populations.

Methods and results: Nine single nucleotide polymorphisms (SNPs) from 9 candidate loci robustly confirmed to be associated with BP in east Asian people, were genotyped. Genotyping was done in up to 17,785 CAD case-control samples (6,522 cases and 11,263 controls). We then tested the associations with other metabolic traits (n≤17,900) and with type 2 diabetes (931 cases and 1,404 controls), and looked up the datasets in silico in other populations. Significant (adjusted P<0.05) CAD associations were found for 5 BP loci: 3 new CAD associations at FIGN,FGF5 and NPR3, and 2 previously reported ones at ATP2B1 and CNNM2. The strongest CAD association was detected at ATP2B1rs2681472 (P=1.7×10(-8)), in the direction inverted to what is generally recognized for BP in the epidemiological studies.CNNM2rs12413409 showed significant association with CAD (P=8.7×10(-7)) and BMI (P=3.5×10(-8), when meta-analyzed with 75,807 east Asian people). The genetic risk score combining BP-raising alleles at each of the SNPs was positively associated with CAD (P=0.011).

Conclusions: A substantial proportion of genetic variants associated with BP were also associated with the risk of CAD in east Asian people, and there was some counter-evidence for causal inference.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian Continental Ancestry Group
  • Blood Pressure / genetics*
  • Cation Transport Proteins
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / physiopathology
  • Cyclins / genetics*
  • Female
  • Genetic Loci*
  • Humans
  • Male
  • Middle Aged
  • Plasma Membrane Calcium-Transporting ATPases / genetics*
  • Polymorphism, Single Nucleotide*

Substances

  • ATP2B1 protein, human
  • CNNM2 protein, human
  • Cation Transport Proteins
  • Cyclins
  • Plasma Membrane Calcium-Transporting ATPases