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 Fietze; Jana 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

doi:10.1371/journal.pgen.1002171

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

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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, …

PLoS Genetics, Vol.7(7)

07/2011

DOI: https://doi.org/10.1371/journal.pgen.1002171

PMID: 21779176

Abstract

Chromosomes, Human, Pair 16

Chromosomes, Human, Pair 2

Genetic Loci

Genetic Predisposition to Disease

Genome-Wide Association Study

Humans

Polymorphism, Single Nucleotide

Reproducibility of Results

Restless Legs Syndrome

Risk Factors

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.

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Title: Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1.
Creators - without role: Juliane Winkelmann - Technical University of Munich
Darina Czamara - Max Planck Institute of Psychiatry
Barbara Schormair - Helmholtz Zentrum München
Franziska Knauf - Institute of Human Genetics
Eva C. Schulte - Technical University of Munich
Claudia Trenkwalder - Paracelsus Elena Klinik Kassel
Yves Dauvilliers - Hôpital Gui de Chauliac
Olli Polo - Tampere University
Birgit Högl - Innsbruck Medical University
Klaus Berger - Institute of Epidemiology and Social Medicine
Andrea Fuhs - Institute of Epidemiology and Social Medicine
Nadine Gross - Department of Neurology
Karin Stiasny-Kolster - Philipps University of Marburg
Wolfgang Oertel - Philipps University of Marburg
Cornelius G. Bachmann - University of Göttingen
Walter Paulus - University of Göttingen
Lan Xiong - Université de Montréal
Jacques Montplaisir - Hôpital du Sacré-Cœur de Montréal
Guy A. Rouleau - Université de Montréal
Ingo Fietze - Charité - Universitätsmedizin Berlin
Jana Vávrová - Charles University
David Kemlink - Charles University
Karel Sonka - Charles University
Sona Nevsimalova - Charles University
Siong-Chi Lin - University of British Columbia
Zbigniew Wszolek - Centre for Molecular Medicine and Therapeutics
Carles Vilariño-Güell - University of British Columbia
Matthew J. Farrer - University of British Columbia
Viola Gschliesser - Innsbruck Medical University
Birgit Frauscher - Innsbruck Medical University
Tina Falkenstetter - Innsbruck Medical University
Werner Poewe - Innsbruck Medical University
Richard P. Allen - Johns Hopkins University
Christopher J. Earley - Johns Hopkins University
William G. Ondo - Baylor College of Medicine
Wei-Dong Le - Baylor College of Medicine
Derek Spieler - Helmholtz Zentrum München
Maria Kaffe - Technical University of Munich
Alexander Zimprich - Medical University of Vienna
Johannes Kettunen - Finnish Institute for Health and Welfare
Markus Perola - Finnish Institute for Health and Welfare
Kaisa Silander - Institute for Molecular Medicine Finland
Isabelle Cournu-Rebeix - Pitié-Salpêtrière Hospital
Marcella Francavilla - Pitié-Salpêtrière Hospital
Claire Fontenille - Inserm
Bertrand Fontaine - Assistance Publique – Hôpitaux de Paris
Pavel Vodicka - Czech Academy of Sciences, Institute of Experimental Medicine
Holger Prokisch - Technical University of Munich
Peter Lichtner - Helmholtz Zentrum München
Paul Peppard - University of Wisconsin–Madison
Juliette Faraco - Stanford University
Emmanuel Mignot - Stanford University
Christian Gieger - Helmholtz Zentrum München
Thomas Illig - Helmholtz Zentrum München
H-Erich Wichmann - Institute of Medical Informatics, Biometry, and Epidemiology
Bertram Müller-Myhsok - Max
Thomas Meitinger - Technical University of Munich
Publication Details: PLoS Genetics, Vol.7(7)
Grant note: The replication phase was supported by a grant from the US RLS Foundation. 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 coworkers, who are responsible for the design and conduction of the KORA studies. The KORA research platform (KORA, Cooperative Research in the Region of Augsburg) was initiated and financed by the Helmholtz Zentrum München, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria. The collection of sociodemographic and clinical data in the Dortmund Health Study was supported by the German Migraine & Headache Society (DMKG) and by unrestricted grants of equal share from Astra Zeneca, Berlin Chemie, Boots Healthcare, Glaxo-Smith-Kline, McNeil Pharma (former Woelm Pharma), MSD Sharp & Dohme, and Pfizer to the University of Muenster. Blood collection in the Dortmund Health Study was done through funds from the Institute of Epidemiology and Social Medicine, University of Muenster. Data collection in the COR-Study was supported by unrestricted grants of the German RLS Society (Deutsche Restless Legs Vereinigung e.V.) and Axxonis Pharma, Boehringer Ingelheim Pharma, Mundipharma Research, Roche Pharma, and UCB to the University of Muenster. CG Bachmann was supported by grants of the German RLS Society, Deutsche Restless Legs Vereinigung, e.V. H Prokisch and T Meitinger were supported by the German Federal Ministry of Education and Research (BMBF) project Systems Biology of Metabotypes (SysMBo #0315494A). RP Allen and CJ Earley were supported by the grant PO1-AG21190 National Institute of Health, USA; the Canadian part of the study was supported by a Canadian Institutes of Health Research (CIHR) grant to GA Rouleau and J Montplaisir. D Kemlink and S Nevsimalova were supported by an ESRS grant MSM0021620849; Jávrová and K Sonka were supported by grant MSM0021620816. Recruitment of Czech controls was funded by grant IGA NR 8563-5, Ministry of Health of the Czech Republic. B Frauscher, I Cournu-Rebeix, M Francavilla, and C Fontenille are co-authors on behalf of BRC-REFGENSEP, which is supported by INSERM, AFM (Généthon), ARSEP, and GIS-IBISA.
Identifiers: 9937753309311
Academic Unit: Institut des Neurosciences de Montpellier - INM
Language: English
Resource Type: Journal article
Local Fields: inserm-00711782