Abstract

We identified association of restless legs syndrome (RLS) with PTPRD at 9p23–24 in 2,458 affected individuals and 4,749 controls from Germany, Austria, Czechia and Canada. Two independent SNPs in the 5′ UTR of splice variants expressed predominantly in the central nervous system showed highly significant P values (rs4626664, Pnominal/λ corrected = 5.91 × 10−10, odds ratio (OR) = 1.44; rs1975197, Pnominal/λ corrected = 5.81 × 10−9, OR = 1.31). This work identifies PTPRD as the fourth genome-wide significant locus for RLS.

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Acknowledgements

We are grateful to all individuals who participated in this study. We wish to thank J. Favor, B. Pütz and K. Oexle for discussions and R. Feldmann, J. Golic, K. Junghans and B. Schmick for technical assistance. We acknowledge L. Habersack, H. Rhese and J. Schmidt-Evers from the German RLS patient organization for supporting this study. Part of this work was financed by the National Genome Research Network (NGFN). The KORA study group consists of H.-E. Wichmann (speaker), R. Holle, J. John, T. Illig, C. Meisinger, A. Peters and their co-workers, who are responsible for the design and conduct of the KORA studies. The KORA research platform (KORA, Cooperative Research in the Region of Augsburg) was initiated and financed by the Helmholtz Zentrum München, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria. The Canadian part of the study was supported by a Canadian Institutes of Health Research (CIHR) grant to G.R., J.M. and G.T. D.K. was supported by grant MSM0021620849, and J.V. and K.S. were supported by grant MSM0021620816. Recruitment of Czech controls was funded by grant IGA NR 8563-5, Ministry of Health of the Czech Republic.

Author information

Author notes

    • Barbara Schormair
    •  & David Kemlink

    These authors contributed equally to this work.

Affiliations

  1. Institute of Human Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg 85764, Germany.

    • Barbara Schormair
    • , David Kemlink
    • , Gertrud Eckstein
    • , Peter Lichtner
    • , Thomas Meitinger
    •  & Juliane Winkelmann
  2. Institute of Human Genetics, Technische Universität München, Munich 81675, Germany.

    • Barbara Schormair
    • , Peter Lichtner
    • , Thomas Meitinger
    •  & Juliane Winkelmann
  3. Department of Neurology, 1st Medical Faculty, Charles University, Prague 120 00, Czech Republic.

    • David Kemlink
    • , Gertrud Eckstein
    • , Jana Vávrová
    • , Karel Sonka
    •  & Sona Nevsimalova
  4. Max Planck Institute of Psychiatry, Munich 80804, Germany.

    • Darina Roeske
    • , Stephan Ripke
    • , Florian Holsboer
    • , Bertram Müller-Myhsok
    •  & Juliane Winkelmann
  5. Centre d'excellence en neuromique, Hôpital Notre-Dame, Université de Montréal, Montréal H2L 4M1, Québec, Canada.

    • Lan Xiong
    •  & Guy Rouleau
  6. Paracelsus-Elena-Hospital, Kassel 34128, Germany.

    • Claudia Trenkwalder
  7. Department of Neurology, Medical University of Vienna, Vienna 1090, Austria.

    • Alexander Zimprich
  8. Department of Neurology, Center of Nervous Diseases, Philipps University, Marburg 35039, Germany.

    • Karin Stiasny-Kolster
    •  & Wolfgang Oertel
  9. Department of Clinical Neurophysiology, University of Göttingen, Göttingen 37070, Germany.

    • Cornelius G Bachmann
    •  & Walter Paulus
  10. Department of Neurology, Innsbruck Medical University, Innsbruck 6020, Austria.

    • Birgit Högl
    • , Birgit Frauscher
    • , Viola Gschliesser
    •  & Werner Poewe
  11. Neurologische Praxis, Berlin 10969, Germany.

    • Ines Peglau
  12. Institute of Experimental Medicine, Czech Academy of Sciences, Prague 140 00, Czech Republic.

    • Pavel Vodicka
  13. Centre d'étude du sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Québec H4J 1C5, Canada.

    • Jacques Montplaisir
  14. Centre de recherche en sciences neurologiques, Université de Montréal, Montréal, Québec H4J 1C5, Canada.

    • Jacques Montplaisir
  15. Departments of Psychiatry and Human Genetics, McGill University, Douglas Hospital, Montreal, Quebec H4H 1R3, Canada.

    • Gustavo Turecki
  16. Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Munich 85764, Germany.

    • Christian Gieger
    • , Thomas Illig
    •  & H-Erich Wichmann
  17. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich 81377, Germany.

    • H-Erich Wichmann
  18. Neurologische Klinik und Poliklinik, Technische Universität München, Ismaninger Strasse 22, 81675 München, Germany.

    • Juliane Winkelmann

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Contributions

Study design: B.M.-M., T.M., J.W. Recruitment and biobanking of RLS cases: C.T., A.Z., K.S.-K., W.O., C.G.B., W. Paulus, B.H., B.F., V.G., W. Poewe, I.P., T.M., J.W. Recruitment and biobanking of KORA controls: C.G., T.I., H.-E.W. Recruitment and biobanking of Canadian RLS cases and controls: L.X., J.M., G.T., G.R. Recruitment and biobanking of Czech RLS cases and controls: D.K., P.V., J.V., K.S., S.N. Affymetrix genotyping: B.S., G.E., P.L. Sequenom genotyping: B.S., D.K., P.L. Supervision of all markers typed: P.L., J.W. Statistical analysis: D.R., S.R., B.M.-M. Clustering of Affymetrix genotypes: D.R., S.R., B.M.-M. Manuscript writing: B.S., D.K., D.R., F.H., B.M.-M., T.M., J.W.

Competing interests

B.S., P.L. B.M.-M., F.H., T.M. and J.W. filed a patent application (application no. 07007202.0-2401) at the European Patent Office. All other authors have no competing financial interests.

Corresponding authors

Correspondence to Thomas Meitinger or Juliane Winkelmann.

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DOI

https://doi.org/10.1038/ng.190

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