IDEAS home Printed from https://ideas.repec.org/a/plo/pgen00/1002171.html
   My bibliography  Save this article

Genome-Wide Association Study Identifies Novel Restless Legs Syndrome Susceptibility Loci on 2p14 and 16q12.1

Author

Listed:
  • 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

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.

Suggested Citation

  • 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, 2011. "Genome-Wide Association Study Identifies Novel Restless Legs Syndrome Susceptibility Loci on 2p14 and 16q12.1," PLOS Genetics, Public Library of Science, vol. 7(7), pages 1-10, July.
  • Handle: RePEc:plo:pgen00:1002171
    DOI: 10.1371/journal.pgen.1002171
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002171
    Download Restriction: no

    File URL: https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002171&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pgen.1002171?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Douglas F. Easton & Karen A. Pooley & Alison M. Dunning & Paul D. P. Pharoah & Deborah Thompson & Dennis G. Ballinger & Jeffery P. Struewing & Jonathan Morrison & Helen Field & Robert Luben & Nicholas, 2007. "Genome-wide association study identifies novel breast cancer susceptibility loci," Nature, Nature, vol. 447(7148), pages 1087-1093, June.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Wei Chen & Wei Wang & Beibei Zhu & Hui Guo & Yu Sun & Jie Ming & Na Shen & Zhi Li & Zhenling Wang & Lifeng Liu & Bingxi Cai & Jiayu Duan & Jiaoyuan Li & Cheng Liu & Rong Zhong & Weiguo Hu & Tao Huang , 2013. "A Functional Variant rs1820453 in YAP1 and Breast Cancer Risk in Chinese Population," PLOS ONE, Public Library of Science, vol. 8(11), pages 1-1, November.
    2. Pei Wang & Shunjie Chen & Sijia Yang, 2022. "Recent Advances on Penalized Regression Models for Biological Data," Mathematics, MDPI, vol. 10(19), pages 1-24, October.
    3. Katherine S Elliott & Eleftheria Zeggini & Mark I McCarthy & Julius Gudmundsson & Patrick Sulem & Simon N Stacey & Steinunn Thorlacius & Laufey Amundadottir & Henrik Grönberg & Jianfeng Xu & Valerie G, 2010. "Evaluation of Association of HNF1B Variants with Diverse Cancers: Collaborative Analysis of Data from 19 Genome-Wide Association Studies," PLOS ONE, Public Library of Science, vol. 5(5), pages 1-8, May.
    4. Guang Guo, 2008. "Introduction to the Special Issue on Society and Genetics," Sociological Methods & Research, , vol. 37(2), pages 159-163, November.
    5. Sharon E Johnatty & Jonathan Beesley & Xiaoqing Chen & Stuart Macgregor & David L Duffy & Amanda B Spurdle & Anna deFazio & Natalie Gava & Penelope M Webb & Australian Ovarian Cancer Study Group & Aus, 2010. "Evaluation of Candidate Stromal Epithelial Cross-Talk Genes Identifies Association between Risk of Serous Ovarian Cancer and TERT, a Cancer Susceptibility “Hot-Spot”," PLOS Genetics, Public Library of Science, vol. 6(7), pages 1-10, July.
    6. Julian Little & Julian PT Higgins & John PA Ioannidis & David Moher & France Gagnon & Erik von Elm & Muin J Khoury & Barbara Cohen & George Davey-Smith & Jeremy Grimshaw & Paul Scheet & Marta Gwinn & , 2009. "STrengthening the REporting of Genetic Association Studies (STREGA)— An Extension of the STROBE Statement," PLOS Medicine, Public Library of Science, vol. 6(2), pages 1-13, February.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pgen00:1002171. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosgenetics (email available below). General contact details of provider: https://journals.plos.org/plosgenetics/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.