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Replication of restless legs syndrome loci in three European populations
  1. D Kemlink1,2,
  2. O Polo3,
  3. B Frauscher4,
  4. V Gschliesser4,
  5. B Högl4,
  6. W Poewe4,
  7. P Vodicka5,
  8. J Vavrova2,
  9. K Sonka2,
  10. S Nevsimalova2,
  11. B Schormair1,6,
  12. P Lichtner1,6,
  13. K Silander7,
  14. L Peltonen7,8,9,10,
  15. C Gieger11,
  16. H E Wichmann11,12,
  17. A Zimprich13,
  18. D Roeske14,
  19. B Müller-Myhsok14,
  20. T Meitinger1,6,
  21. J Winkelmann1,6,15
  1. 1
    Helmholtz Zentrum Munich, National Research Center of Environment and Health, Institute of Human Genetics, Munich, Germany
  2. 2
    Department of Neurology, Charles University in Prague, 1st Faculty of Medicine and General Teaching Hospital, (Kateřinská 30, Prague), Czech Republic
  3. 3
    University of Turku Sleep Research Unit, Turku, Finland
  4. 4
    University Clinic Innsbruck, Department of Neurology, Innsbruck, Austria
  5. 5
    Institute of Experimental Medicine, Czech Academy of Sciences, Prague, Czech Republic
  6. 6
    Technische Universität, Institute of Human Genetics, Munich, Germany
  7. 7
    Department of Chronic Disease Prevention, National Institute for Health and Welfare, and FIMM, Institute for Molecular Medicine Finland, Helsinki, Finland
  8. 8
    Department of Medical Genetics, University of Helsinki, Helsinki, Finland
  9. 9
    The Broad Institute of MIT and Harvard, Boston, Massachusetts, USA
  10. 10
    Department of Human Genetics, Wellcome Trust Sanger Institute, Cambridge, UK
  11. 11
    Institute of Epidemiology, Helmholtz Zentrum Munich, National Research Center for Environment and Health, Munich, Germany
  12. 12
    Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany
  13. 13
    Department of Neurology, Medical University of Vienna, Austria
  14. 14
    Max-Planck-Institute of Psychiatry, Munich, Germany
  15. 15
    Technische Universität, Neurological Clinic, Munich, Germany
  1. Dr J Winkelmann, Klinik für Neurologie and Institut für Humangenetik, Klinikum rechts der Isar, Technische Universität München (TUM), Ismaninger Strasse 22, 81675 München, Germany; winkelmann{at}


Background: Restless legs syndrome (RLS) is associated with common variants in three intronic and intergenic regions in MEIS1, BTBD9, and MAP2K5/LBXCOR1 on chromosomes 2p, 6p and 15q.

Methods: Our study investigated these variants in 649 RLS patients and 1230 controls from the Czech Republic (290 cases and 450 controls), Austria (269 cases and 611 controls) and Finland (90 cases and 169 controls). Ten single nucleotide polymorphisms (SNPs) within the three genomic regions were selected according to the results of previous genome-wide scans. Samples were genotyped using Sequenom platforms.

Results: We replicated associations for all loci in the combined samples set (rs2300478 in MEIS1, p = 1.26×10−5, odds ratio (OR) = 1.47, rs3923809 in BTBD9, p = 4.11×10−5, OR = 1.58 and rs6494696 in MAP2K5/LBXCOR1, p = 0.04764, OR = 1.27). Analysing only familial cases against all controls, all three loci were significantly associated. Using sporadic cases only, we could confirm the association only with BTBD9.

Conclusion: Our study shows that variants in these three loci confer consistent disease risks in patients of European descent. Among the known loci, BTBD9 seems to be the most consistent in its effect on RLS across populations and is also most independent of familial clustering.

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  • Funding: KS and JV were supported by a grant MSM0021620816. The group of Czech healthy controls was recruited and sampled within the frame of grant IGA NR 8563-5, Ministry of Health of the Czech Republic.

  • Competing interests: None.

  • Patient consent: Obtained.