Genome-Wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1

Juliane Winkelmann, Darina Czamara, Barbara Schormair, Franziska Knauf, Eva C. Schulte, Claudia Trenkwalder, Yves Dauvilliers, Olli Polo, Birgit Högl, Klaus Berger, Andrea Fuhs, Nadine Gross, Karin Stiasny-Kolster, Wolfgang Oertel, Cornelius G. Bachmann, Walter Paulus, Lan Xiong, Jacques Montplaisir, Guy A. Rouleau, Ingo FietzeJana Vávrová, David Kemlink, Karel Sonka, Sona Nevsimalova, Siong Chi Lin, Zbigniew Wszolek, Carles Vilariño-Güell, Matthew J. Farrer, Viola Gschliesser, Birgit Frauscher, Tina Falkenstetter, Werner Poewe, Richard P. Allen, Christopher J. Earley, William G. Ondo, Wei Dong Le, Derek Spieler, Maria Kaffe, Alexander Zimprich, Johannes Kettunen, Markus Perola, Kaisa Silander, Isabelle Cournu-Rebeix, Marcella Francavilla, Claire Fontenille, Bertrand Fontaine, Pavel Vodicka, Holger Prokisch, Peter Lichtner, Paul Peppard, Juliette Faraco, Emmanuel Mignot, Christian Gieger, Thomas Illig, H. Erich Wichmann, Bertram Müller-Myhsok, Thomas Meitinger

Research output: Contribution to journalArticlepeer-review

134 Scopus citations


Restless legs syndrome (RLS) is a sensorimotor disorder with an age-dependent prevalence of up to 10% in the general population above 65 years of age. Affected individuals suffer from uncomfortable sensations and an urge to move in the lower limbs that occurs mainly in resting situations during the evening or at night. Moving the legs or walking leads to an improvement of symptoms. Concomitantly, patients report sleep disturbances with consequences such as reduced daytime functioning. We conducted a genome-wide association study (GWA) for RLS in 922 cases and 1,526 controls (using 301,406 SNPs) followed by a replication of 76 candidate SNPs in 3,935 cases and 5,754 controls, all of European ancestry. Herein, we identified six RLS susceptibility loci of genome-wide significance, two of them novel: an intergenic region on chromosome 2p14 (rs6747972, P = 9.03 × 10 -11, OR = 1.23) and a locus on 16q12.1 (rs3104767, P = 9.4 × 10 -19, OR = 1.35) in a linkage disequilibrium block of 140 kb containing the 5′-end of TOX3 and the adjacent non-coding RNA BC034767.

Original languageEnglish (US)
Article numbere1002171
JournalPLoS genetics
Issue number7
StatePublished - Jul 2011
Externally publishedYes

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research


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