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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Change history
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.
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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.
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Deng, M., Wei, L., Zuo, X. et al. Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis. Nat Genet 45, 697–700 (2013). https://doi.org/10.1038/ng.2627
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