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

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 casecontrol 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 ATP2B1 rs2681472 (P=1.7×10^–8), in the direction inverted to what is generally recognized for BP in the epidemiological studies. CNNM2 rs12413409 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.