Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease

Abstract

We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases and 5,019 controls followed by replication studies in 15,460 cases and 11,472 controls, all of Chinese Han ancestry. We identify four new loci for coronary artery disease that reached the threshold of genome-wide significance (P < 5 × 10(-8)). These loci mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1. We also replicated four loci previously identified in European populations (in or near PHACTR1, TCF21, CDKN2A-CDKN2B and C12orf51). These findings provide new insights into pathways contributing to the susceptibility for coronary artery disease in the Chinese Han population.

Figure 1

Regional association plots of four new loci. (a-d) In the top panel of each, SNPs are plotted according to their chromosomal positions (NCBI build36) with their P values (as −log₁₀ P values) of the discovery meta-analysis. The lead SNP is represented by a purple diamond with the discovery meta-analysis result, and represented by a purple circle with the combined analysis result denoted by P_combined value. The r² values of LD between the lead SNP and the other SNPs are indicated by different colors. The estimated recombination rates from 1000 Genomes June 2010 CHB+JPT samples are plotted in cyan to reflect the local LD structure. In the bottom panels the genes within the region of interest are annotated and are shown as arrows. Plots were generated using LocusZoom (see URLs).

Figure 2

CAD risk score categories and risk of CAD. This figure shows odds ratios for CAD compared with quintile 3 as solid dot with whiskers extending to OR±95%CI. The white and gray bars represent number of controls and cases in each quintile. This analysis was performed in 15,591 individuals (7,012 cases and 8,579 controls) with all phenotype information for nine SNPs in Table 1 and Supplementary Table 3, including rs2123536, rs1842896, rs9349379, rs9268402, rs12524865, rs10757274, rs1333042, rs7136259, and rs11066280.