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Full sequencing and haplotype analysis of MAPT in Parkinson's disease and rapid eye movement sleep behavior disorder
Authors:Jiao Li MD  Jennifer A. Ruskey MSc  Isabelle Arnulf MD  PhD  Yves Dauvilliers MD  PhD  Michele T.M. Hu MBBS  FRCP   PhD  Birgit Högl MD  Claire S. Leblond PhD  Sirui Zhou PhD  Amirthagowri Ambalavanan PhD  Jay P. Ross BSc  Cynthia V. Bourassa MSc  Dan Spiegelman MSc  Sandra B Laurent  Ambra Stefani MD  Christelle Charley Monaca MD  PhD  Valérie Cochen De Cock MD  PhD  Michel Boivin PhD  Luigi Ferini‐Strambi MD  PhD  Giuseppe Plazzi MD  PhD  Elena Antelmi MD  PhD  Peter Young MD  Anna Heidbreder MD  Catherine Labbe PhD  Tanis J. Ferman PhD  Patrick A. Dion PhD  Dongsheng Fan MD  PhD  Alex Desautels MD  PhD  Jean‐François Gagnon PhD  Nicolas Dupré MD  MSc  Edward A. Fon  Jacques Y. Montplaisir MD  PhD  Bradley F. Boeve MD  Ronald B. Postuma MD  MSc  Guy A. Rouleau MD  PhD  Owen A. Ross PhD  Ziv Gan‐Or MD  PhD
Affiliation:1. Department of Neurology, Peking University Third Hospital, Beijing, China;2. Montreal Neurological Institute, McGill University, Montréal, QC, Canada;3. Department of Neurology and neurosurgery, McGill University, Montréal, QC, Canada;4. Sleep Disorders Unit, Pitié Salpêtrière Hospital, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière and Sorbonne Universities, UPMC Paris 6 univ, Paris, France;5. Sleep Unit, National Reference Network for Narcolepsy, Department of Neurology H?pital‐Gui‐de Chauliac, CHU Montpellier, INSERM U1061, Montpellier, France;6. Oxford Parkinson's Disease Centre (OPDC), University of Oxford, Oxford, United Kingdom;7. Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom;8. Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria;9. Department of Human Genetics, McGill University, Montréal, QC, Canada;10. University Lille north of France, Department of clinical neurophysiology and sleep center, CHU Lille, Lille, France;11. Sleep and neurology unit, Beau Soleil Clinic, Montpellier, France;12. EuroMov, University of Montpellier, Montpellier, France;13. GRIP, école de psychologie, Université Laval, Québec city, QC, Canada;14. Institute of Genetic, Neurobiological and Social Foundations of Child Development, Tomsk State University, Tomsk, Russia;15. Department of Neurological Sciences, Università Vita‐Salute San Raffaele, Milan, Italy;16. Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum, University of Bologna, Bologna, Italy;17. IRCCS, Institute of Neurological Sciences of Bologna, Bologna, Italy;18. Department of Sleep Medicine and Neuromuscular Disorders, University of Muenster, Muenster, Germany;19. Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, Florida, USA;20. Centre d'études Avancées en Médecine du Sommeil, H?pital du Sacré‐C?ur de Montréal, Montréal, QC, Canada;21. Department of Neurosciences, Université de Montréal, Montréal, QC, Canada;22. Département de psychologie, Université du Québec à Montréal, Montréal, QC, Canada;23. Division of Neurosciences, CHU de Québec, Université Laval, Quebec City, QC, Canada;24. Department of Medicine, Faculty of Medicine, Université Laval, Quebec City, QC, Canada;25. Department of Psychiatry, Université de Montréal, Montréal, QC, Canada;26. Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA;27. Department of Neurology, Montreal General Hospital, Montréal, QC, Canada;28. Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA;29. Department of Clinical Genomics, Mayo Clinic, Jacksonville, Florida, USA
Abstract:Background: MAPT haplotypes are associated with PD, but their association with rapid eye movement sleep behavior disorder is unclear. Objective: To study the role of MAPT variants in rapid eye movement sleep behavior disorder. Methods: Two cohorts were included: (A) PD (n = 600), rapid eye movement sleep behavior disorder (n = 613) patients, and controls (n = 981); (B) dementia with Lewy bodies patients with rapid eye movement sleep behavior disorder (n = 271) and controls (n = 950). MAPT‐associated variants and the entire coding sequence of MAPT were analyzed. Age‐, sex‐, and ethnicity‐adjusted analyses were performed to examine the association between MAPT, PD, and rapid eye movement sleep behavior disorder. Results: MAPT‐H2 variants were associated with PD (odds ratios: 0.62‐0.65; P = 0.010‐0.019), but not with rapid eye movement sleep behavior disorder. In PD, the H1 haplotype odds ratio was 1.60 (95% confidence interval: 1.12‐2.28; P = 0.009), and the H2 odds ratio was 0.68 (95% confidence interval: 0.48‐0.96; P = 0.03). The H2/H1 haplotypes were not associated with rapid eye movement sleep behavior disorder. Conclusions: Our results confirm the protective effect of the MAPT‐H2 haplotype in PD, and define its components. Furthermore, our results suggest that MAPT does not play a major role in rapid eye movement sleep behavior disorder, emphasizing different genetic background than in PD in this locus. © 2018 International Parkinson and Movement Disorder Society
Keywords:REM sleep behavior disorder  Parkinson's disease  genetics  MAPT
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