TY - JOUR
T1 - Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions
AU - Winkelmann, Juliane
AU - Schormair, Barbara
AU - Lichtner, Peter
AU - Ripke, Stephan
AU - Xiong, Lan
AU - Jalilzadeh, Shapour
AU - Fulda, Stephany
AU - Pütz, Benno
AU - Eckstein, Gertrud
AU - Hauk, Stephanie
AU - Trenkwalder, Claudia
AU - Zimprich, Alexander
AU - Stiasny-Kolster, Karin
AU - Oertel, Wolfgang
AU - Bachmann, Cornelius G.
AU - Paulus, Walter
AU - Peglau, Ines
AU - Eisensehr, Ilonka
AU - Montplaisir, Jacques
AU - Turecki, Gustavo
AU - Rouleau, Guy
AU - Gieger, Christian
AU - Illig, Thomas
AU - Wichmann, H. Erich
AU - Holsboer, Florian
AU - Müller-Myhsok, Bertram
AU - Meitinger, Thomas
N1 - Funding Information:
We are grateful to all patients who participated in this study. The authors also thank T.M. Strom, J. Favor, D. Vogt-Weisenhorn, W. Wurst and I. Tews for discussions and R. Feldmann, J. Golic, K. Junghans, B. Schmick, N. Trapp, M. Petzold, G. Fischer and M. Putz 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 (Cooperative Research in the Region of Augsburg) research project was initiated and financed by the National Research Centre for Environment and Health (GSF), which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria. S.H. was partly supported by a grant from the German RLS patient organization. J.W. was partly supported by a grant form the Bavarian Ministry of Science, Culture and Art. The Canadian
Funding Information:
part of the study was supported by a Canadian Institutes of Health Research (CIHR) grant to G.R, J.M and G.T.
PY - 2007/8
Y1 - 2007/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34547497308&partnerID=8YFLogxK
U2 - 10.1038/ng2099
DO - 10.1038/ng2099
M3 - Article
C2 - 17637780
AN - SCOPUS:34547497308
SN - 1061-4036
VL - 39
SP - 1000
EP - 1006
JO - Nature Genetics
JF - Nature Genetics
IS - 8
ER -