 Genome-Wide Association Study Identifies Novel Restless Legs Syndrome Susceptibility Loci on 2p14 and 16q12.1Juliane 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 and Thomas Meitinger PLOS Genetics, 2011, vol. 7, issue 7, 1-10 Abstract: 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. Author Summary: Restless legs syndrome (RLS) is one of the most common neurological disorders. Patients with RLS suffer from an urge to move the legs and unpleasant sensations located mostly deep in the calf. Symptoms mainly occur in resting situations in the evening or at night. As a consequence, initiation and maintenance of sleep become defective. Here, we performed a genome-wide association study to identify common genetic variants increasing the risk for disease. The genome-wide phase included 922 cases and 1,526 controls, and candidate SNPs were replicated in 3,935 cases and 5,754 controls, all of European ancestry. We identified two new RLS–associated loci: an intergenic region on chromosome 2p14 and a locus on 16q12.1 in a linkage disequilibrium block containing the 5′-end of TOX3 and the adjacent non-coding RNA BC034767. TOX3 has been implicated in the development of breast cancer. The physiologic role of TOX3 and BC034767 in the central nervous system and a possible involvement of these two genes in RLS pathogenesis remain to be established. Date: 2011 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:plo:pgen00:1002171 DOI: 10.1371/journal.pgen.1002171 Access Statistics for this article More articles in PLOS Genetics from Public Library of Science |
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