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Parkinson’s Disease Genetic Loci in Rapid Eye Movement Sleep Behavior Disorder

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Abstract

Rapid eye movement (REM) sleep behavior disorder (RBD) is a prodromal condition for Parkinson’s disease (PD) and other synucleinopathies, which often occurs many years before the onset of PD. We analyzed 261 RBD patients and 379 controls for nine PD-associated SNPs and examined their effects, first upon on RBD risk and second, on eventual progression to synucleinopathies in a prospective follow-up in a subset of patients. The SCARB2 rs6812193 (OR = 0.67, 95 % CI = 0.51–0.88, p = 0.004) and the MAPT rs12185268 (OR–0.43, 95 % CI–0.26–0.72, p = 0.001) were associated with RBD in different models. Kaplan-Meier survival analysis in a subset of RBD patients (n = 56), demonstrated that homozygous carriers of the USP25 rs2823357 SNP had progressed to synucleinopathies faster than others (log-rank p = 0.003, Breslow p = 0.005, Tarone-Ware p = 0.004). As a proof-of-concept study, these results suggest that RBD may be associated with at least a subset of PD-associated genes, and demonstrate that combining genetic and prodromal clinical data may help identifying individuals that are either more or less susceptible to develop synucleinopathies. More studies are necessary to replicate these results, and identify more genetic factors affecting progression from RBD to synucleinopathies.

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Acknowledgments

We would like to thank the patients for their participating in this study. This work was financially supported by the Parkinson Society of Canada and by the Michael J Fox Foundation. ZGO is supported by a postdoctoral fellowship from the Canadian Institutes of Health Research (CIHR). JFG is supported by grants from CIHR and Fonds de Recherche Santé Québec (FRSQ). JM is supported by grants from CIHR. GAR holds a Canada Research Chair in Genetics of the Nervous System and the Wilder Pennfield Chair in Neurosciences.

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    Authors and Affiliations

    1. Montreal Neurological Institute and McGill University, Montréal, QC, Canada

      Z. Gan-Or, S. L. Girard, A. Noreau, C. S. Leblond, C. Mirarchi, P. A. Dion & G. A. Rouleau

    2. Département de Psychologie, Université du Québec à Montréal, Montréal, QC, Canada

      J. F. Gagnon

    3. Centre d’Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, QC, Canada

      J. F. Gagnon, A. Desautels & J. Y. Montplaisir

    4. Sleep Disorders Unit, Pitié Salpêtrière Hospital, Brain and Spine Institute and Sorbonne Universities, Paris, France

      I. Arnulf

    5. Sleep Unit, National Reference Network for Narcolepsy, Department of Neurology Hôpital-Gui-de Chauliac, CHU, Montpellier, France

      Y. Dauvilliers

    6. Department of Neurosciences, Université de Montréal, Montréal, Canada

      A. Desautels

    7. Sleep Disorders Clinic, Department of Neurology, Innsbruck Medical University, Innsbruck, Austria

      T. Mitterling, B. Frauscher & B. Hogl

    8. Pôle Sommeil, Clinique Beau Soleil, Montpellier, France

      V. Cochen De Cock

    9. EuroMov, Laboratoire Movement to Health (M2H), University of Montpellier, Montpellier, France

      V. Cochen De Cock

    10. Centre d’Investigation Clinique, Hôpital Saint Eloi, Montpellier, France

      V. Cochen De Cock & C. Monaca

    11. Department of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada

      P. A. Dion & G. A. Rouleau

    12. Department of Neurology, Montreal General Hospital, Montréal, QC, Canada

      R. B. Postuma

    13. Department of Psychiatry, Université de Montréal, Montréal, QC, Canada

      J. Y. Montplaisir

    14. Montréal Neurological Institute and Hospital, 3801, University Street, Office 636, Montréal, Québec, H3A 2B4, Canada

      G. A. Rouleau

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    1. Z. Gan-Or
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    2. S. L. Girard
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    Correspondence to G. A. Rouleau.

    Additional information

    Z. Gan-Or and S. L. Girard contributed equally to this work.

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    Gan-Or, Z., Girard, S.L., Noreau, A. et al. Parkinson’s Disease Genetic Loci in Rapid Eye Movement Sleep Behavior Disorder. J Mol Neurosci 56, 617–622 (2015). https://doi.org/10.1007/s12031-015-0569-7

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    • DOI: https://doi.org/10.1007/s12031-015-0569-7

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