• A Corrigendum to this article was published on 29 May 2013

This article has been updated

Abstract

To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, Pcombined = 2.92 × 10−8, odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, Pcombined = 2.35 × 10−9, OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.

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  • 09 May 2013

    In the version of this article initially published online, the affiliations of authors Xiuxiu Liu, Xiaogang Li, Nan Zhang and Na Liu were incorrect. The correct affiliation of these authors is the Department of Neurology, Peking University Third Hospital, Beijing, China. The errors have been corrected in the PDF, HTML and print versions of this article.

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Acknowledgements

We thank all participants in this study and all neurologists at relevant hospitals for their help in the recruitment of subjects, including Peking University Third Hospital and the First Affiliated Hospital of Anhui Medical University. This study was funded by the Key Project of the National Natural Science Foundation of China (91232717), the National Basic Research Program of China (2011CB707805), the National Natural Science Foundation of China (81171273, 31000528, 81100806, 31100812, 31000503 and 81070877) and the Special Research Fund for the Doctoral Program of Higher Education (20113420110001) and was also supported by the National Nature Science Foundation of China (31171048, 81072374, 30973043 and 30700906), the Science and Technology New Star Funds of Beijing (2007A008 and 2009A04), the Beijing Science Foundation (7112146 and 7102159), the Beijing Nova Program (2009A04 and 2007A008) and A*STAR of Singapore.

Author information

Author notes

    • Min Deng
    • , Ling Wei
    • , Xianbo Zuo
    •  & Yanghua Tian

    These authors contributed equally to this work.

Affiliations

  1. Medical Research Center, Peking University Third Hospital, Beijing, China.

    • Min Deng
  2. Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei, China.

    • Ling Wei
    • , Yanghua Tian
    • , Fei Xie
    • , Panpan Hu
    • , Chunyan Zhu
    • , Fengqiong Yu
    • , Yu Meng
    • , Honghao Wang
    • , Fangfang Zhang
    • , Huijuan Ma
    • , Rong Ye
    • , Wenwen Dong
    • , Shanshan Zhou
    • , Changqing Wang
    • , Yu Wang
    • , Jingye Wang
    • , Xianwen Chen
    • , Zhongwu Sun
    • , Nong Zhou
    • , Yubao Jiang
    •  & Kai Wang
  3. Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, China.

    • Xianbo Zuo
    • , Yong Cui
    • , Xianyong Yin
    • , Hui Cheng
    • , Bo Liang
    • , Xiaodong Zheng
    • , Gang Chen
    • , Fusheng Zhou
    • , Liangdan Sun
    • , Sen Yang
    •  & Xuejun Zhang
  4. State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Hefei, China.

    • Xianbo Zuo
    • , Yong Cui
    • , Xianyong Yin
    • , Hui Cheng
    • , Bo Liang
    • , Xiaodong Zheng
    • , Gang Chen
    • , Fusheng Zhou
    • , Liangdan Sun
    • , Sen Yang
    •  & Xuejun Zhang
  5. Department of Neurology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.

    • Huaidong Cheng
    •  & Jing Du
  6. Department of Neurology, Peking University Third Hospital, Beijing, China.

    • Xiuxiu Liu
    • , Xiaogang Li
    • , Nan Zhang
    •  & Na Liu
  7. Department of Histology and Embryology, Weifang Medical University, Weifang, China.

    • Yingjun Guan
  8. Institution of Neurology, Anhui College of Traditional Medicine, Hefei, China.

    • Yongsheng Han
    •  & Yongzhu Han
  9. Department of Neurology, Anhui Provincial Hospital, Hefei, China.

    • Xinyi Lv
    •  & Yu Fu
  10. Department of Neurology, Suzhou First People's Hospital, Suzhou, China.

    • Hui Yu
  11. Department of Neurology, the Third Affiliated Hospital of Anhui Medical University, Hefei, China.

    • Chunhua Xi
  12. Department of Neurology, Anqing City Hospital, Anqing, China.

    • Dandan Xie
  13. Department of Neurology, Lu'an First People's Hospital, Lu'an, China.

    • Qiyuan Zhao
  14. Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

    • Peng Xie
  15. Department of Neurology, Zhongshan Hospital of Fudan University, Shanghai, China.

    • Xin Wang
  16. Department of Neuropsychiatry, Institute of Neuropsychiatry of Southeast University, Nanjing, China.

    • Zhijun Zhang
  17. Department of Neurology, Xiangya Hospital of Central South University, Changsha, China.

    • Lu Shen
    •  & Beisha Tang
  18. Laboratory of Neuropsychology, Hong Kong University, Hong Kong, China.

    • Tatia M C Lee
  19. Department of Neurology, Rudolf, University Medical Center, Utrecht, The Netherlands.

    • Jan H Veldink
    •  & Leonard H van den Berg
  20. Department of Neurology, Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium.

    • Wim Robberecht
  21. Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.

    • John E Landers
  22. Institute of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.

    • Peter M Andersen
  23. Department of Clinical Neuroscience, Medical Research Council Centre for Neurodegeneration Research, Institute of Psychiatry, King's College London, London, UK.

    • Ammar Al-Chalabi
    •  & Chris Shaw
  24. Department of Neurology, Second Affiliated Hospital, Soochow University, Suzhou, China.

    • Chunfeng Liu
  25. Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.

    • Shangxi Xiao
    •  & Janice Robertson
  26. Clinical Brain Disorder Branch, National Institute of Mental Health, Bethesda, Maryland, USA.

    • Fengyu Zhang
  27. School of Life Sciences, Anhui Medical University, Hefei, China.

    • Jianjun Liu
  28. Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.

    • Jianjun Liu
  29. Saw Swee Hock School of Public Health, National University of Singapore, Singapore.

    • Jianjun Liu
  30. Institute of Sports Medicine, Peking University Third Hospital, Beijing, China.

    • Xiaodong Ju

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Contributions

K.W. and M.D. conceived this study. X. Zhang, K.W. and M.D. provided financial support. K.W., M.D., L.W., X. Zuo, Y.T. and X.J. designed the study. P.H., H.W., H.M., T.M.C.L. and Y.M. took part in the design of the study and in sample selection. M.D., Y.T., X.J., Yongzhu Han, Yongsheng Han, X. Lv, Y.F., H.Y., C.X., J.D., D.X., C.Z., F.Y., R.Y., Q.Z., C.L., B.T., X. Li, N. Zhou, Huaidong Cheng, W.D., Fangfang Zhang, J.E.L., S.Z., C.W., Y.W., J.W., X.C., Z.S., N. Zhang, X. Liu, Y.J., P.X., Z.Z., L. Shen, X.W. and N.L. conducted sample selection and data management. L.W., F.X., G.C., Y.C., Hui Cheng and X.J. collected phenotype data for the GWAS. L.W., F. Zhou, X.Y., Y.G. and X. Li collected phenotype data for the validation stage. L.H.v.d.B., J.H.V., W.R., J.R., P.M.A., A.A.-C. and C.S. collected the phenotype data for the validation stage in individuals of European ancestry. X. Zuo, B.L., X. Zheng and L.W. collected phenotype data, undertook related data handling and calculation, managed recruitment and obtained biological samples. X. Zuo, S.Y., L. Sun, Fengyu Zhang, J.L., S.X. and J.R. undertook data checking, statistical analysis and bioinformatics analyses. K.W., X. Zhang, X. Zuo, X.J. and M.D. were responsible for project management. L.S. and J.L. helped to revise the manuscript. All authors contributed to the final manuscript. K.W., M.D., L.W., X. Zuo, Y.T., X.J., L.S. and X.Z. had a key role in the study.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Xiaodong Ju or Kai Wang.

Supplementary information

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DOI

https://doi.org/10.1038/ng.2627

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