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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.

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Figure 1: Regional plots of the four loci newly associated with CAD.
Figure 2: CAD risk score categories and risk for CAD.

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Acknowledgements

This study was funded by the National Basic Research Program of China (973 Plan) (2011CB503901 and 2006CB503805) from the Ministry of Science and Technology of China, by the National Science Foundation of China (30930047), by the High-Tech Research and Development Program of China (863 Plan) (2009AA022703, 2012AA02A516 and 2006AA02A406) and by a grant from the Ministry of Science and Technology of China (2006BAI01A01). This study was also supported by Biomedical Project from the Council of Science and Technology, Beijing (H020220030130).

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D. Gu conceived of and designed the study and supervised all the sample selection, genotyping, data analysis and interpretation. B.Q., Depei Liu and X. Peng participated in the study design and interpretation. Genotyping experiments were performed by S.C., Y.S., L. Zhang and H.L. under the supervision of D. Gu, L.H., J. Cheng and L.C. DNA sample preparation was carried out by Laiyuan Wang, H.L., T.W., Y.M., Q.Z., Yun Li, D.Y., Q.W., Ying Yang, F. Liu, Q. Mao, X. Liang, J.J., X.M., D. Li, Xuehui Liu and C.D. Phenotype collection and data management were conducted by J.H., S.C., J.L., J. Cao, Jichun Chen, Donghua Liu, Jingping Chen, X.D., T.W., Ligui Wang, Y.M., Z.F., Ying Li, L. Zhao, X.Z., F. Lu, Z.L., C.Y., C.S., X. Pu, L.Y., X.F., L.X., J.M., Xianping Wu, R.Z., N.W., Xiaoli Liu, M.W., D.H., X.J., D. Guo, D.S., P.C., G.C., Xigui Wu, L.C., Yuejin Yang, Y.T., X. Li, Z.D., Z.Y., Q. Meng, D.W., R.W. and J.Y. H.S., N.J.S., S.K., M.P.R. and J.E. provided the data from the CARDIoGRAM Consortium. Statistical analysis was performed by X. Lu, X.Y., Y.H., D. Ge, C.C.G. and R.C. The manuscript was written by D. Gu, X. Lu and Laiyuan Wang. All authors reviewed the manuscript.

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Correspondence to Dongfeng Gu.

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Supplementary Figures 1–5, Supplementary Tables 1–9 and Supplementary Note (PDF 724 kb)

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Lu, X., Wang, L., Chen, S. et al. Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease. Nat Genet 44, 890–894 (2012). https://doi.org/10.1038/ng.2337

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