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Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis

Nature Genetics volume 40, pages 29–31 (2008)Cite this article

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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Figure 1: Schematic overview of DPP6.

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References

  1. Rowland, L.P. & Shneider, N.A. N. Engl. J. Med. 344, 1688–1700 (2001).

    Article  CAS  Google Scholar 

  2. Pasinelli, P. & Brown, R.H. Nat. Rev. Neurosci. 7, 710–723 (2006).

    Article  CAS  Google Scholar 

  3. Graham, A.J., Macdonald, A.M. & Hawkes, C.H. J. Neurol. Neurosurg. Psychiatry 62, 562–569 (1997).

    Article  CAS  Google Scholar 

  4. Greenway, M.J. et al. Nat. Genet. 38, 411–413 (2006).

    Article  CAS  Google Scholar 

  5. Lambrechts, D. et al. Nat. Genet. 34, 383–394 (2003).

    Article  CAS  Google Scholar 

  6. Sutedja, N.A. et al. Arch. Neurol. 64, 63–67 (2007).

    Article  Google Scholar 

  7. Saeed, M. et al. Neurology 67, 771–776 (2006).

    Article  CAS  Google Scholar 

  8. Veldink, J.H. et al. Neurology 65, 820–825 (2005).

    Article  CAS  Google Scholar 

  9. Schymick, J.C. et al. Lancet Neurol. 6, 322–328 (2007).

    Article  CAS  Google Scholar 

  10. Skol, A.D., Scott, L.J., Abecasis, G.R. & Boehnke, M. Nat. Genet. 38, 209–213 (2006).

    Article  CAS  Google Scholar 

  11. Zaitlen, N., Kang, H.M., Eskin, E. & Halperin, E. Am. J. Hum. Genet. 80, 683–691 (2007).

    Article  CAS  Google Scholar 

  12. Wada, K. et al. Mamm. Genome 4, 234–237 (1993).

    Article  CAS  Google Scholar 

  13. Tachibana, T., Noguchi, K. & Ruda, M.A. Neurosci. Lett. 327, 133–137 (2002).

    Article  CAS  Google Scholar 

  14. Dorus, S. et al. Cell 119, 1027–1040 (2004).

    Article  CAS  Google Scholar 

Download references

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.

Author information

Author notes

  1. Michael A van Es, Paul WJ van Vught, Hylke M Blauw and Lude Franke: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands

    Michael A van Es, Paul WJ van Vught, Hylke M Blauw, Christiaan GJ Saris, Sonja W de Jong, John HJ Wokke, Jan H Veldink & Leonard H van den Berg

  2. Department of Biomedical Genetics, Complex Genetics Section, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands

    Lude Franke, Ruben van't Slot & Cisca Wijmenga

  3. Department of Neurology, University Hospital Gasthuisberg, Leuven, B-3000, Belgium

    Ludo Van Den Bosch, Robin Lemmens & Wim Robberecht

  4. Department of Neurology, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands

    Vianney de Jong

  5. Department of Neurogenetics, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands

    Frank Baas

  6. Department of Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, 6525 GA, The Netherlands

    Helenius J Schelhaas

  7. Institute of Clinical Neuroscience, Umeå University Hospital, Umeå, SE-901 85, Sweden

    Anna Birve & Peter M Andersen

  8. Department of Molecular Genetics, Neurodegenerative Brain Diseases Group, VIB, Antwerpen, B-2610, Belgium

    Kristel Sleegers & Christine Van Broeckhoven

  9. University of Antwerp, Antwerpen, B-2610, Belgium

    Kristel Sleegers & Christine Van Broeckhoven

  10. Laboratory of Neurogenetics, National Institute of Aging, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Jennifer C Schymick

  11. Section on Developmental Genetic Epidemiology, National Institute of Mental Health, Bethesda, 20892, Maryland, USA

    Bryan J Traynor

  12. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB, The Netherlands

    Cisca Wijmenga

  13. Department of Medical Genetics and Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands

    Roel A Ophoff

  14. Neuropsychiatric Institute, University of California, Los Angeles, 90095, California, USA

    Roel A Ophoff

Authors
  1. Michael A van Es
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  2. Paul WJ van Vught
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  4. Lude Franke
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  12. Helenius J Schelhaas
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  13. Anna Birve
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  16. Jennifer C Schymick
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  20. Wim Robberecht
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  21. Peter M Andersen
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  22. Jan H Veldink
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  23. Roel A Ophoff
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  24. Leonard H van den Berg
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Contributions

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.

Corresponding authors

Correspondence to Roel A Ophoff or Leonard H van den Berg.

Supplementary information

Supplementary Text and Figures

Supplementary Methods, Supplementary Tables 1–5, Supplementary Figures 1–3 (PDF 885 kb)

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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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