title: Genetic markers of Restless Legs Syndrome in Parkinson disease.
abstract: BACKGROUND
  Several studies proposed that Restless Legs Syndrome (RLS) and Parkinson disease (PD) may be clinically and/or etiologically related. To examine this hypothesis, we aimed to determine whether the known RLS genetic markers may be associated with PD risk, as well as with PD subtype.
  
  
  METHODS
  Two case-control cohorts from Tel-Aviv and New-York, including 1133 PD patients and 867 controls were genotyped for four RLS-related SNPs in the genes MEIS1, BTBD9, PTPRD and MAP2K5/SKOR1. The association between genotype, PD risk and phenotype was tested using multivariate regression models.
  
  
  RESULTS
  None of the tested SNPs was significantly associated with PD risk, neither in any individual cohort nor in the combined analysis after correction for multiple comparisons. The MAP2K5/SKOR1 marker rs12593813 was associated with higher frequency of tremor in the Tel-Aviv cohort (61.0% vs. 46.5%, p = 0.001, dominant model). However, the risk allele for tremor in this gene has been associated with reduced RLS risk. Moreover, this association did not replicate in Tremor-dominant PD patients from New-York.
  
  
  CONCLUSIONS
  RLS genetic risk markers are not associated with increased PD risk or subtype in the current study. Together with previous genetic, neuropathological and epidemiologic studies, our results further strengthen the notion that RLS and PD are likely to be distinct entities.
authors: Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Department of Human Genetics, McGill University, Montréal, QC, Canada.
authors: Ziv
authors: Z
authors: Gan-Or
authors: Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors: Roy N
authors: RN
authors: Alcalay
authors: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors: Anat
authors: A
authors: Bar-Shira
authors: Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Department of Human Genetics, McGill University, Montréal, QC, Canada.
authors: Claire S
authors: CS
authors: Leblond
authors: Department of Neurology, Montreal General Hospital, Montréal, QC, Canada.
authors: Ronald B
authors: RB
authors: Postuma
authors: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors: Shay
authors: S
authors: Ben-Shachar
authors: Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors: Cheryl
authors: C
authors: Waters
authors: Laboratory of Neurogenetics, Research Centre, Montreal Mental Health University Institute, Montréal, QC, Canada.
authors: Amelie
authors: A
authors: Johnson
authors: Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors: Oren
authors: O
authors: Levy
authors: Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors: Anat
authors: A
authors: Mirelman
authors: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors: Mali
authors: M
authors: Gana-Weisz
authors: Faculté de Médecine, Université Laval, CHU de Québec (Enfant-Jésus), Québec, QC, Canada.
authors: Nicolas
authors: N
authors: Dupré
authors: Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, QC, Canada; Department of Psychiatry, Université de Montréal, Montréal, QC, Canada.
authors: Jacques
authors: J
authors: Montplaisir
authors: Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.
authors: Nir
authors: N
authors: Giladi
authors: Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors: Stanley
authors: S
authors: Fahn
authors: Laboratory of Neurogenetics, Research Centre, Montreal Mental Health University Institute, Montréal, QC, Canada; Department of Psychiatry, Université de Montréal, Montréal, QC, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada.
authors: Lan
authors: L
authors: Xiong
authors: Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada.
authors: Patrick A
authors: PA
authors: Dion
authors: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel; Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.
authors: Avi
authors: A
authors: Orr-Urtreger
authors: Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada. Electronic address: guy.rouleau@mcgill.ca.
authors: Guy A
authors: GA
authors: Rouleau
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D048671:MAP Kinase Kinase 5 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics; D012148:Restless Legs Syndrome / Q000235:genetics*; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics
chemical_list: C522207:BTBD9 protein, human; D005819:Genetic Markers; D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D048671:MAP Kinase Kinase 5; C482563:MAP2K5 protein, human; C090899:PTPRD protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
keywords: Genetics; Parkinson disease; Restless Legs Syndrome