Letter abstract


Nature Genetics 39, 1000 - 1006 (2007)
Published online: 18 July 2007 | doi:10.1038/ng2099

Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions

Juliane Winkelmann1,2,3, Barbara Schormair1,3, Peter Lichtner1,3, Stephan Ripke2, Lan Xiong4, Shapour Jalilzadeh1,3, Stephany Fulda2, Benno Pütz2, Gertrud Eckstein1,3, Stephanie Hauk1,3, Claudia Trenkwalder5, Alexander Zimprich6, Karin Stiasny-Kolster7, Wolfgang Oertel7, Cornelius G Bachmann8, Walter Paulus8, Ines Peglau9, Ilonka Eisensehr10, Jacques Montplaisir11,12, Gustavo Turecki13, Guy Rouleau4, Christian Gieger14, Thomas Illig14, H-Erich Wichmann14,15, Florian Holsboer2, Bertram Müller-Myhsok2,16 & Thomas Meitinger1,3,16

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Restless legs syndrome (RLS) is a frequent neurological disorder characterized by an imperative urge to move the legs during night, unpleasant sensation in the lower limbs, disturbed sleep and increased cardiovascular morbidity. In a genome-wide association study we found highly significant associations between RLS and intronic variants in the homeobox gene MEIS1, the BTBD9 gene encoding a BTB(POZ) domain as well as variants in a third locus containing the genes encoding mitogen-activated protein kinase MAP2K5 and the transcription factor LBXCOR1 on chromosomes 2p, 6p and 15q, respectively. Two independent replications confirmed these association signals. Each genetic variant was associated with a more than 50% increase in risk for RLS, with the combined allelic variants conferring more than half of the risk. MEIS1 has been implicated in limb development, raising the possibility that RLS has components of a developmental disorder.

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  1. Institute of Human Genetics, GSF National Research Center of Environment and Health, D-85764 Neuherberg, Munich, Germany.
  2. Max Planck Institute of Psychiatry, D-80804 Munich, Germany.
  3. Technical University, Institute of Human Genetics, D-81675 Munich, Germany.
  4. Laboratoire d'étude des maladies du cerveau, Centre de recherche du CHUM, Hôpital Notre-Dame, Université de Montréal, Montréal, Québec H2L 4M1, Canada.
  5. Paracelsus-Elena-Hospital, 34128 Kassel, Germany.
  6. Neurological Department, Medical University of Vienna, 1090 Vienna, Austria.
  7. Philipps University Marburg, Department of Neurology, 35039 Marburg, Germany.
  8. University of Göttingen, Department of Clinical Neurophysiology, 37070 Göttingen, Germany.
  9. Neurologische Praxis, 10969 Berlin, Germany.
  10. Neurologische Praxis Sendlingerstrasse, 80331 Munich, Germany.
  11. Centre d'étude du sommeil, Hôpital du Sacré-Co eligur de Montréal, Montréal, Québec H4J 1C5, Canada.
  12. Centre de recherche en sciences neurologiques, Université de Montréal, Montréal, Québec H4J 1C5, Canada.
  13. Departments of Psychiatry and Human Genetics, McGill University, Douglas Hospital, Montreal, Quebec H4H 1R3, Canada.
  14. Institute of Epidemiology, GSF National Research Center for Environment and Health, 85764 Neuherberg, Munich, Germany.
  15. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, 81377 Munich, Germany.
  16. These authors contributed equally to this work.

Correspondence to: Juliane Winkelmann1,2,3 e-mail: janew@mpipsykl.mpg.de

Correspondence to: Thomas Meitinger1,3,16 e-mail: meitinger@gsf.de



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