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

Nature Genetics volume 44, pages 890894 (2012) | Download Citation

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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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).

Author information

Author notes

    • Xiangfeng Lu
    •  & Laiyuan Wang

    These authors contributed equally to this work.

Affiliations

  1. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

    • Xiangfeng Lu
    • , Laiyuan Wang
    • , Shufeng Chen
    • , Xueli Yang
    • , Jianfeng Huang
    • , Jianxin Li
    • , Jie Cao
    • , Jichun Chen
    • , Dongliang Ge
    • , Ying Li
    • , Liancheng Zhao
    • , Lanying Chen
    • , Donghua Liu
    • , Jingping Chen
    • , Xiufang Duan
    • , Yongchen Hao
    • , Qi Zhao
    • , Dahai Yu
    • , Qianqian Wang
    • , Ying Yang
    • , Fangchao Liu
    • , Qunxia Mao
    • , Xiaohua Liang
    • , Jingfeng Ji
    • , Xingbo Mo
    • , Dianjiang Li
    • , Guoping Chai
    • , Xiangdong Li
    • , Zhenhan Du
    • , Xigui Wu
    •  & Dongfeng Gu
  2. National Human Genome Center at Beijing, Beijing, China.

    • Laiyuan Wang
    • , Hongfan Li
    • , Xuehui Liu
    •  & Chenlong Dou
  3. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.

    • Lin He
    •  & Yongyong Shi
  4. National Engineering Research Center for Beijing Biochip Technology (NERCBBT), Beijing, China.

    • Jing Cheng
    •  & Liang Zhang
  5. Medical Systems Biology Research Center, School of Medicine, Tsinghua University, Beijing, China.

    • Jing Cheng
  6. Division of Biostatistics, Washington University School of Medicine, St Louis, Missouri, USA.

    • C Charles Gu
  7. Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China.

    • Tangchun Wu
    •  & Ligui Wang
  8. Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumchi, China.

    • Yitong Ma
  9. Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

    • Zhongjie Fan
  10. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

    • Xiaoyang Zhou
  11. Cardio-Cerebrovascular Control and Research Center, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China.

    • Fanghong Lu
    •  & Zhendong Liu
  12. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.

    • Cailiang Yao
    •  & Chong Shen
  13. Department of Cardiology, Fujian Provincial People's Hospital, Fuzhou, China.

    • Xiaodong Pu
    •  & Lin Yu
  14. Department of Epidemiology and Social Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.

    • Xianghua Fang
  15. Department of Cardiology, The Affiliated Hospital of Beihua University, Beihua University, Jilin, China.

    • Lihua Xu
  16. Department of Cardiology, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China.

    • Jianjun Mu
  17. Center for Chronic and Noncommunicable Disease Control and Prevention, Sichuan Center of Disease Control and Prevention, Chengdu, China.

    • Xianping Wu
  18. Cardiovascular Disease Prevention Center, Shougang Hospital, Peking University, Beijing, China.

    • Runping Zheng
  19. Department of Cardiology, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

    • Naqiong Wu
    • , Yida Tang
    •  & Yuejin Yang
  20. School of Public Health, Hebei United University, Tangshan, China.

    • Yun Li
  21. Department of Cardiology, Anzhen Hospital, Capital Medical University, Beijing, China.

    • Xiaoli Liu
  22. Department of Emergency Medicine, Beijing Jishuitan Hospital, Beijing, China.

    • Mengqin Wang
  23. School of Public Health, Zhengzhou University, Zhengzhou, China.

    • Dongsheng Hu
  24. School of Medicine, Shenzhen University, Shenzhen, China.

    • Dongsheng Hu
  25. Department of Internal Medicine, Xinle Red Cross Hospital, Xinle, China.

    • Xu Ji
  26. Department of Internal Medicine, Yuxian Renmin Hospital, Yuxian, China.

    • Dongshuang Guo
  27. Institute of Geriatrics, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

    • Dongling Sun
  28. Renqiu Heath Bureau, Renqiu, China.

    • Panpan Chen
  29. Nantong Center of Disease Control and Prevention, Nantong, China.

    • Zili Yang
  30. Zhangqiu Heath Bureau, Zhangqiu, China.

    • Qingjie Meng
  31. Xin'an Heath Bureau, Xin'an, China.

    • Dong Wang
  32. Department of Internal Medicine, Shijiazhuang Greatwall Hospital, Shijiazhuang, China.

    • Renping Wang
  33. Department of Cardiology, Hanzhong Renmin Hospital, Hanzhong, China.

    • Jun Yang
  34. Medizinische Klinik II, Universität zu Lübeck, Lübeck, Germany.

    • Heribert Schunkert
    •  & Jeanette Erdmann
  35. Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), Universität zu Lübeck, Lübeck, Germany.

    • Heribert Schunkert
    •  & Jeanette Erdmann
  36. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK.

    • Nilesh J Samani
  37. Leicester National Institute for Health Research, Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, UK.

    • Nilesh J Samani
  38. Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Sekar Kathiresan
  39. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Sekar Kathiresan
  40. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

    • Sekar Kathiresan
  41. The Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Muredach P Reilly
  42. Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

    • Xiaozhong Peng
    • , Depei Liu
    •  & Boqin Qiang
  43. Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

    • Runsheng Chen

Consortia

  1. The Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Consortium

    A full list of members and affiliations is provided in the Supplementary Note.

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Contributions

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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Dongfeng Gu.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–5, Supplementary Tables 1–9 and Supplementary Note

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DOI

https://doi.org/10.1038/ng.2337

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