Ziv Gan-Or1, Roy N Alcalay2, Anat Bar-Shira3, Claire S Leblond1, Ronald B Postuma4, Shay Ben-Shachar3, Cheryl Waters2, Amelie Johnson5, Oren Levy2, Anat Mirelman6, Mali Gana-Weisz3, Nicolas Dupré7, Jacques Montplaisir8, Nir Giladi9, Stanley Fahn2, Lan Xiong10, Patrick A Dion11, Avi Orr-Urtreger12, Guy A Rouleau13. 1. Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Department of Human Genetics, McGill University, Montréal, QC, Canada. 2. 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. 3. The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. 4. Department of Neurology, Montreal General Hospital, Montréal, QC, Canada. 5. Laboratory of Neurogenetics, Research Centre, Montreal Mental Health University Institute, Montréal, QC, Canada. 6. Department of Neurology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. 7. Faculté de Médecine, Université Laval, CHU de Québec (Enfant-Jésus), Québec, QC, Canada. 8. 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. 9. 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. 10. 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. 11. Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada. 12. 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. 13. Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada. Electronic address: guy.rouleau@mcgill.ca.
Abstract
INTRODUCTION: 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. CONCLUSION: 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.
INTRODUCTION: 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 PDpatients 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 PDpatients from New-York. CONCLUSION: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.
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