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

Juliane Winkelmann, Barbara Schormair, Peter Lichtner, Stephan Ripke, Lan Xiong, Shapour Jalilzadeh, Stephany Fulda, Benno Pütz, Gertrud Eckstein, Stephanie Hauk, Claudia Trenkwalder, Alexander Zimprich, Karin Stiasny-Kolster, Wolfgang Oertel, Cornelius G. Bachmann, Walter Paulus, Ines Peglau, Ilonka Eisensehr, Jacques Montplaisir, Gustavo TureckiGuy Rouleau, Christian Gieger, Thomas Illig, H. Erich Wichmann, Florian Holsboer, Bertram Müller-Myhsok, Thomas Meitinger

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569 Scopus citations


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.

Original languageEnglish
Pages (from-to)1000-1006
Number of pages7
JournalNature Genetics
Issue number8
StatePublished - Aug 2007


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