Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions - PubMed (original) (raw)

doi: 10.1038/ng2099. Epub 2007 Jul 18.

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 Turecki, Guy Rouleau, Christian Gieger, Thomas Illig, H-Erich Wichmann, Florian Holsboer, Bertram Müller-Myhsok, Thomas Meitinger

Affiliations

• PMID: 17637780
• DOI: 10.1038/ng2099

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

Juliane Winkelmann et al. Nat Genet. 2007 Aug.

Abstract

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.

PubMed Disclaimer

Comment in

• A step forward for restless legs syndrome.
  Mignot E. Mignot E. Nat Genet. 2007 Aug;39(8):938-9. doi: 10.1038/ng0807-938. Nat Genet. 2007. PMID: 17660808 No abstract available.

Similar articles

• Replication of restless legs syndrome loci in three European populations.
  Kemlink D, Polo O, Frauscher B, Gschliesser V, Högl B, Poewe W, Vodicka P, Vavrova J, Sonka K, Nevsimalova S, Schormair B, Lichtner P, Silander K, Peltonen L, Gieger C, Wichmann HE, Zimprich A, Roeske D, Müller-Myhsok B, Meitinger T, Winkelmann J. Kemlink D, et al. J Med Genet. 2009 May;46(5):315-8. doi: 10.1136/jmg.2008.062992. Epub 2009 Mar 10. J Med Genet. 2009. PMID: 19279021 Free PMC article.
• A direct interaction between two Restless Legs Syndrome predisposing genes: MEIS1 and SKOR1.
  Catoire H, Sarayloo F, Mourabit Amari K, Apuzzo S, Grant A, Rochefort D, Xiong L, Montplaisir J, Earley CJ, Turecki G, Dion PA, Rouleau GA. Catoire H, et al. Sci Rep. 2018 Aug 15;8(1):12173. doi: 10.1038/s41598-018-30665-6. Sci Rep. 2018. PMID: 30111810 Free PMC article.
• Association studies of variants in MEIS1, BTBD9, and MAP2K5/SKOR1 with restless legs syndrome in a US population.
  Yang Q, Li L, Chen Q, Foldvary-Schaefer N, Ondo WG, Wang QK. Yang Q, et al. Sleep Med. 2011 Sep;12(8):800-4. doi: 10.1016/j.sleep.2011.06.006. Sleep Med. 2011. PMID: 21925394 Free PMC article.
• Genetics of restless legs syndrome.
  Winkelmann J. Winkelmann J. Curr Neurol Neurosci Rep. 2008 May;8(3):211-6. doi: 10.1007/s11910-008-0033-y. Curr Neurol Neurosci Rep. 2008. PMID: 18541116 Review.
• [Pathophysiology of restless legs syndrome].
  Miyamoto M, Miyamoto T, Iwanami M, Suzuki K, Hirata K. Miyamoto M, et al. Brain Nerve. 2009 May;61(5):523-32. Brain Nerve. 2009. PMID: 19514512 Review. Japanese.

Cited by

• Genome-wide association study of sleep in Drosophila melanogaster.
  Harbison ST, McCoy LJ, Mackay TF. Harbison ST, et al. BMC Genomics. 2013 Apr 25;14:281. doi: 10.1186/1471-2164-14-281. BMC Genomics. 2013. PMID: 23617951 Free PMC article.
• Ropinirole in restless legs syndrome and periodic limb movement disorder.
  Erichsen D, Ferri R, Gozal D. Erichsen D, et al. Ther Clin Risk Manag. 2010 Apr 15;6:173-82. doi: 10.2147/tcrm.s6717. Ther Clin Risk Manag. 2010. PMID: 20421915 Free PMC article.
• Depressive disorders in restless legs syndrome: epidemiology, pathophysiology and management.
  Hornyak M. Hornyak M. CNS Drugs. 2010 Feb;24(2):89-98. doi: 10.2165/11317500-000000000-00000. CNS Drugs. 2010. PMID: 20088617
• A HapMap harvest of insights into the genetics of common disease.
  Manolio TA, Brooks LD, Collins FS. Manolio TA, et al. J Clin Invest. 2008 May;118(5):1590-605. doi: 10.1172/JCI34772. J Clin Invest. 2008. PMID: 18451988 Free PMC article. Review.
• Probable RBD Associates with the Development of RLS in Parkinson's Disease: A Cross-Sectional Study.
  Qu Y, Zhang L, Shen D, Zhang W, Zhang M, Pan Y. Qu Y, et al. Behav Neurol. 2019 Apr 1;2019:7470904. doi: 10.1155/2019/7470904. eCollection 2019. Behav Neurol. 2019. PMID: 31065297 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group

• Other Literature Sources

  • H1 Connect
  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Molecular Biology Databases

  • GlyGen glycoinformatics resource

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal