SMPD1 variants do not have a major role in rapid eye movement sleep behavior disorder

Uladzislau Rudakou; Naomi C Futhey; Lynne Krohn; Jennifer A Ruskey; Karl Heilbron; Paul Cannon; 23andMe Research Team; Armaghan Alam; Isabelle Arnulf; Michele T M Hu; Jacques Y Montplaisir; Jean-François Gagnon; Alex Desautels; Yves Dauvilliers; Marco Toffoli; Gian Luigi Gigli; Mariarosaria Valente; Birgit Högl; Ambra Stefani; Evi Holzknecht; Karel Sonka; David Kemlink; Wolfang Oertel; Annette Janzen; Giuseppe Plazzi; Elena Antelmi; Michela Figorilli; Monica Puligheddu; Brit Mollenhauer; Claudia Trenkwalder; Friederike Sixel-Döring; Valérie Cochen De Cock; Christelle Charley Monaca; Anna Heidbreder; Luigi Ferini-Strambi; Femke Dijkstra; Mineke Viaene; Beatriz Abril; Bradley F Boeve; Ronald B Postuma; Guy A Rouleau; Ziv Gan-Or

doi:10.1016/j.neurobiolaging.2020.04.005

SMPD1 variants do not have a major role in rapid eye movement sleep behavior disorder

Neurobiol Aging. 2020 Sep:93:142.e5-142.e7. doi: 10.1016/j.neurobiolaging.2020.04.005. Epub 2020 Apr 18.

Authors

Uladzislau Rudakou¹, Naomi C Futhey², Lynne Krohn¹, Jennifer A Ruskey³, Karl Heilbron⁴, Paul Cannon⁴; 23andMe Research Team⁴; Armaghan Alam², Isabelle Arnulf⁵, Michele T M Hu⁶, Jacques Y Montplaisir⁷, Jean-François Gagnon⁸, Alex Desautels⁹, Yves Dauvilliers¹⁰, Marco Toffoli¹¹, Gian Luigi Gigli¹², Mariarosaria Valente¹³, Birgit Högl¹⁴, Ambra Stefani¹⁴, Evi Holzknecht¹⁴, Karel Sonka¹⁵, David Kemlink¹⁵, Wolfang Oertel¹⁶, Annette Janzen¹⁶, Giuseppe Plazzi¹⁷, Elena Antelmi¹⁷, Michela Figorilli¹⁸, Monica Puligheddu¹⁸, Brit Mollenhauer¹⁹, Claudia Trenkwalder¹⁹, Friederike Sixel-Döring²⁰, Valérie Cochen De Cock²¹, Christelle Charley Monaca²², Anna Heidbreder²³, Luigi Ferini-Strambi²⁴, Femke Dijkstra²⁵, Mineke Viaene²⁵, Beatriz Abril²⁶, Bradley F Boeve²⁷, Ronald B Postuma²⁸, Guy A Rouleau²⁹, Ziv Gan-Or³⁰

Affiliations

¹ Department of Human Genetics, McGill University, Montréal, Quebec, Canada; Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada.
² Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada.
³ Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada.
⁴ 23andMe, Inc., Sunnyvale, CA, USA.
⁵ Sleep Disorders Unit, Pitié Salpêtrière Hospital, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, Sorbonne University, Paris, France.
⁶ Oxford Parkinson's Disease Centre (OPDC), University of Oxford, Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
⁷ Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada; Department of Psychiatry, Université de Montréal, Montréal, Quebec, Canada.
⁸ Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada; Department of Psychology, Université du Québec à Montréal, Montréal, Quebec, Canada.
⁹ Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada; Department of Neurosciences, Université de Montréal, Montréal, Quebec, Canada.
¹⁰ National Reference Center for Narcolepsy, Sleep Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU Montpellier, University of Montpellier, Inserm U1061, Montpellier, France.
¹¹ Department of Medicine (DAME), University of Udine, Udine, Italy; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
¹² Clinical Neurology Unit, Department of Neurosciences, University Hospital of Udine, Udine, Italy; DMIF, University of Udine, Udine, Italy.
¹³ Department of Medicine (DAME), University of Udine, Udine, Italy; Clinical Neurology Unit, Department of Neurosciences, University Hospital of Udine, Udine, Italy.
¹⁴ Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
¹⁵ Department of Neurology and Centre of Clinical Neuroscience, Charles University, First Faculty of Medicine and General University Hospital, Prague, Czech Republic.
¹⁶ Department of Neurology, Philipps-University Marburg, Marburg, Germany.
¹⁷ Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum, University of Bologna, Bologna, Italy; IRCCS, Institute of Neurological Sciences of Bologna, Bologna, Italy.
¹⁸ Department of Medical Sciences and Public Health, Sleep Disorder Research Center, University of Cagliari, Cagliari, Italy.
¹⁹ Paracelsus-Elena-Klinik, Kassel, Germany; Department of Neurology, University Medical Centre Goettingen, Goettingen, Germany.
²⁰ Department of Neurology, Philipps-University Marburg, Marburg, Germany; Paracelsus-Elena-Klinik, Kassel, Germany.
²¹ Sleep and Neurology Unit, Beau Soleil Clinic, Montpellier, France; EuroMov, University of Montpellier, Montpellier, France.
²² University Lille North of France, Department of Clinical Neurophysiology and Sleep Center, CHU Lille, Lille, France.
²³ Department of Sleep Medicine and Neuromuscular Disorders, University of Muenster, Muenster, Germany.
²⁴ Department of Neurological Sciences, Università Vita-Salute San Raffaele, Milan, Italy.
²⁵ Laboratory for Sleep Disorders, St. Dimpna Regional Hospital, Geel, Belgium; Department of Neurology, St. Dimpna Regional Hospital, Geel, Belgium.
²⁶ Sleep Disorder Unit, Carémeau Hospital, University Hospital of Nîmes, Nîmes, France.
²⁷ Department of Neurology, Mayo Clinic, Rochester, MN, USA.
²⁸ Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada; Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Quebec, Canada.
²⁹ Department of Human Genetics, McGill University, Montréal, Quebec, Canada; Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada.
³⁰ Department of Human Genetics, McGill University, Montréal, Quebec, Canada; Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montréal, Quebec, Canada. Electronic address: ziv.gan-or@mcgill.ca.

PMID: 32409254
DOI: 10.1016/j.neurobiolaging.2020.04.005

Abstract

Mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene were reported to be associated with Parkinson's disease and dementia with Lewy bodies. In the current study, we aimed to evaluate the role of SMPD1 variants in isolated rapid eye movement sleep behavior disorder (iRBD). SMPD1 and its untranslated regions were sequenced using targeted next-generation sequencing in 959 iRBD patients and 1287 controls from European descent. Our study reports no statistically significant association of SMPD1 variants and iRBD. It is hence unlikely that SMPD1 plays a major role in iRBD.

Keywords: Association study; REM sleep behavior disorder; Sphingomyelin phosphodiesterase 1.

MeSH terms

Female
Genetic Association Studies*
Genetic Variation*
High-Throughput Nucleotide Sequencing
Humans
Male
Negative Results*
Sleep Wake Disorders / genetics*
Sleep Wake Disorders / physiopathology*
Sleep, REM / genetics*
Sphingomyelin Phosphodiesterase / genetics*
Sphingomyelin Phosphodiesterase / physiology

Substances

SMPD1 protein, human
Sphingomyelin Phosphodiesterase

Abstract

MeSH terms

Substances

Grants and funding