title: Association of restless legs syndrome variants in Korean patients with restless legs syndrome.
abstract: OBJECTIVE
  Recent genome-wide association studies (GWAS) for Caucasians identified several allelic variants associated with increased risk of developing restless legs syndrome (RLS), also known as Willis-Ekbom disease. Although the pathogenic mechanisms of RLS are not entirely understood, it is becoming increasingly evident that many diseases such as RLS can be attributed to an epistasis. The study objectives were to evaluate whether the associations of RLS with all loci determined in previous GWAS for Caucasians can be replicated significantly for the Korean population and to elucidate whether an epistasis plays a role in the pathogenesis of RLS.
  
  
  METHODS
  DNA from 320 patients with RLS and 320 age- and sex-matched controls were genotyped for variants in the RLS loci.
  
  
  RESULTS
  A significant association was found for rs3923809 and rs9296249 in BTBD9 (P < 0.0001 and P = 0.001, respectively); the odds ratio (OR) for rs3923809 was 1.61 (P < 0.0001) to 1.88 (P < 0.0001) and the OR for rs9296249 was 1.44 (P = 0.001) to 1.73 (P = 0.002), according to the model of inheritance. The OR for the interaction between rs3923809 in BTBD9 and rs4626664 in PTPRD was 2.05 (P < 0.0001) in the additive model, 1.80 (P = 0.002) in the dominant model and 2.47 (P = 0.004) in the recessive model. There was no significant association between genotypes of all tested single nucleotide polymorphisms and the mean value of serum iron parameters.
  
  
  CONCLUSIONS
  Our results suggest that the role of BTBD9 in the pathogenesis of restless legs syndrome is more universal across populations than previously reported and more efforts should be focused on the role of epistasis in the genetic architecture of restless legs syndrome.
authors.affiliation: Department of Neurology, The Brain Korea 21 Project, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Myeong-Kyu
authors.initials: MK
authors.lastname: Kim
authors.forename: Yong Won
authors.initials: YW
authors.lastname: Cho
authors.forename: Won Chul
authors.initials: WC
authors.lastname: Shin
authors.forename: Jae Wook
authors.initials: JW
authors.lastname: Cho
authors.forename: Young Min
authors.initials: YM
authors.lastname: Shon
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Kwang Ik
authors.initials: KI
authors.lastname: Yang
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Earley
authors.forename: Richard P
authors.initials: RP
authors.lastname: Allen
mesh_terms: D004843:Epistasis, Genetic / Q000235:genetics; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D056910:Republic of Korea / Q000453:epidemiology; D012148:Restless Legs Syndrome / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
chemical_list: C522207:BTBD9 protein, human; D009419:Nerve Tissue Proteins; D014157:Transcription Factors
keywords: BTBD9; PTPRD; epistasis; restless legs syndrome