Abstract
We identified a SNP in the DPP6 gene that is consistently strongly associated with susceptibility to amyotrophic lateral sclerosis (ALS) in different populations of European ancestry, with an overall P value of 5.04 × 10−8 in 1,767 cases and 1,916 healthy controls and with an odds ratio of 1.30 (95% confidence interval (CI) of 1.18–1.43). Our finding is the first report of a genome-wide significant association with sporadic ALS and may be a target for future functional studies.
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Acknowledgements
We are indebted to the individuals and their families who participated in this project. This project has been generously supported by The Netherlands Organisation for Scientific Research (NWO) and the “Prinses Beatrix Fonds” (L.H.vdB.). We would also like to thank H. Kersten and M. Kersten for their generous support (L.H.vdB.) as well as J.R. van Dijk and the Adessium foundation (L.H.vdB.), the US National Institutes of Health grants GM68875 and MH078075 (R.A.O.), the Kempe Foundation (P.M.A.), the Swedish Brain Research Foundation and Bertil Hållsten (P.M.A.), the Björklund Foundation for ALS Research (P.M.A.), the Interuniversity Attraction Pole Programme P6/43 (Belgian Science Policy Office) (W.R., L.V.D.B. and C.V.B.) and the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders (W.R.). C.V.B., W.R. and L.V.D.B. are supported by the Fund for Scientific Research Flanders (FWO-F), and K.S. holds a postdoctoral fellowship of the FWO-F. P.M.A. and A.B. are supported by the 'Swedish Brain Power Foundation'. This study used data from the SNP Database at the US National Institute of Neurological Disorders and Stroke Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds/). The authors thank E. Strengman, P. Sodaar, H. Veldman, H. Yigittop, W. Scheveneels, A. D'hondt, P. Tilkin and A. Nilsson for assistance with genotyping and DNA preparation. We also thank F.G. Jennekens and G. Hille Ris Lambers for helping with the DNA sample collection.
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M.A.vE., P.W.J.vV., H.M.B. and L.F. contributed equally to this study. M.A.vE., P.W.J.vV., H.M.B. and R.vS. participated in the Illumina and TaqMan SNP genotyping and data analysis. M.A.vE., J.H.V. and L.F. were involved in the design of the study, handled genotype data and performed statistical analyses. M.A.vE., H.M.B., C.G.J.S., P.M.A., L.V.D.B., S.W.dJ., A.B., R.L., V.dJ., F.B., H.J.S., K.S., C.V.B., J.H.J.W., C.W. and W.R. were responsible for DNA collection and clinical characterization of affected individuals in the study. J.C.S. and B.J.T. obtained all DNA samples from the United States and performed genotyping experiments and analysis on these samples. M.A.vE. drafted the manuscript. R.A.O. and L.H.vdB. are lead investigators and contributed equally to this work. They designed and supervised the study and contributed in the writing of the manuscript. All authors participated in the critical revisions of the manuscript.
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van Es, M., van Vught, P., Blauw, H. et al. Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis. Nat Genet 40, 29–31 (2008). https://doi.org/10.1038/ng.2007.52
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DOI: https://doi.org/10.1038/ng.2007.52
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