Heterogeneous Effects of Association Between Blood Pressure Loci and Coronary Artery Disease in East Asian Individuals

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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 atFIGN,FGF5andNPR3, and 2 previously reported ones atATP2B1andCNNM2. The strongest CAD association was detected atATP2B1rs2681472 (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.