Jiao Li1,2, Jennifer A Ruskey2,3, Isabelle Arnulf4, Yves Dauvilliers5, Michele T M Hu6,7, Birgit Högl8, Claire S Leblond2,9, Sirui Zhou2,3, Amirthagowri Ambalavanan2,3, Jay P Ross2,9, Cynthia V Bourassa2,3, Dan Spiegelman2,3, Sandra B Laurent2,3, Ambra Stefani8, Christelle Charley Monaca10, Valérie Cochen De Cock11,12, Michel Boivin13,14, Luigi Ferini-Strambi15, Giuseppe Plazzi16,17, Elena Antelmi16,17, Peter Young18, Anna Heidbreder18, Catherine Labbe19, Tanis J Ferman19, Patrick A Dion2,3, Dongsheng Fan1, Alex Desautels20,21, Jean-François Gagnon20,22, Nicolas Dupré23,24, Edward A Fon2,3, Jacques Y Montplaisir20,25, Bradley F Boeve26, Ronald B Postuma2,3,27, Guy A Rouleau2,3,9, Owen A Ross28,29, Ziv Gan-Or2,3,9. 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 Hôpital-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, H3A 0G4, 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, Hôpital du Sacré-Cœur 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.
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.
Authors: Michael G Heckman; Koji Kasanuki; Rebecca R Brennan; Catherine Labbé; Emily R Vargas; Alexandra I Soto; Melissa E Murray; Shunsuke Koga; Dennis W Dickson; Owen A Ross Journal: Mov Disord Date: 2019-06-24 Impact factor: 10.338
Authors: Uladzislau Rudakou; Eric Yu; Lynne Krohn; Jennifer A Ruskey; Farnaz Asayesh; Yves Dauvilliers; Dan Spiegelman; Lior Greenbaum; Stanley Fahn; Cheryl H Waters; Nicolas Dupré; Guy A Rouleau; Sharon Hassin-Baer; Edward A Fon; Roy N Alcalay; Ziv Gan-Or Journal: Brain Date: 2021-03-03 Impact factor: 13.501
Authors: Mitchell G Miglis; Charles H Adler; Elena Antelmi; Dario Arnaldi; Luca Baldelli; Bradley F Boeve; Matteo Cesari; Irene Dall'Antonia; Nico J Diederich; Kathrin Doppler; Petr Dušek; Raffaele Ferri; Jean-François Gagnon; Ziv Gan-Or; Wiebke Hermann; Birgit Högl; Michele T Hu; Alex Iranzo; Annette Janzen; Anastasia Kuzkina; Jee-Young Lee; Klaus L Leenders; Simon J G Lewis; Claudio Liguori; Jun Liu; Christine Lo; Kaylena A Ehgoetz Martens; Jiri Nepozitek; Giuseppe Plazzi; Federica Provini; Monica Puligheddu; Michal Rolinski; Jan Rusz; Ambra Stefani; Rebekah L S Summers; Dallah Yoo; Jennifer Zitser; Wolfgang H Oertel Journal: Lancet Neurol Date: 2021-08 Impact factor: 44.182
Authors: Lynne Krohn; Richard Y J Wu; Karl Heilbron; Jennifer A Ruskey; Sandra B Laurent; Cornelis Blauwendraat; Armaghan Alam; Isabelle Arnulf; Michele T M Hu; Yves Dauvilliers; Birgit Högl; Mathias Toft; Kari Anne Bjørnarå; Ambra Stefani; Evi Holzknecht; Christelle Charley Monaca; Beatriz Abril; Giuseppe Plazzi; Elena Antelmi; Luigi Ferini-Strambi; Peter Young; Anna Heidbreder; Valérie Cochen De Cock; Brit Mollenhauer; Friederike Sixel-Döring; Claudia Trenkwalder; Karel Sonka; David Kemlink; Michela Figorilli; Monica Puligheddu; Femke Dijkstra; Mineke Viaene; Wolfang Oertel; Marco Toffoli; Gian Luigi Gigli; Mariarosaria Valente; Jean-François Gagnon; Mike A Nalls; Andrew B Singleton; Alex Desautels; Jacques Y Montplaisir; Paul Cannon; Owen A Ross; Bradley F Boeve; Nicolas Dupré; Edward A Fon; Ronald B Postuma; Lasse Pihlstrøm; Guy A Rouleau; Ziv Gan-Or Journal: Ann Neurol Date: 2020-02-12 Impact factor: 11.274
Authors: Ziv Gan-Or; Trisha Rao; Etienne Leveille; Clotilde Degroot; Sylvain Chouinard; Francesca Cicchetti; Alain Dagher; Samir Das; Alex Desautels; Janelle Drouin-Ouellet; Thomas Durcan; Jean-François Gagnon; Angela Genge; Jason Karamchandani; Anne-Louise Lafontaine; Sonia Lai Wing Sun; Mélanie Langlois; Martin Levesque; Calvin Melmed; Michel Panisset; Martin Parent; Jean-Baptiste Poline; Ronald B Postuma; Emmanuelle Pourcher; Guy A Rouleau; Madeleine Sharp; Oury Monchi; Nicolas Dupré; Edward A Fon Journal: J Parkinsons Dis Date: 2020 Impact factor: 5.568