NPC1 encodes a lysosomal protein involved in cholesterol transport. Biallelic mutations in this gene may lead to Niemann-Pick disease type C (NPC), a lysosomal storage disorder. The role of NPC1 in alpha synucleinopathies is still unclear, as different genetic, clinical, and pathological studies have reported contradictory results. This study aimed to evaluate the association of NPC1 variants with the synucleinopathies Parkinson's disease (PD), dementia with Lewy bodies (DLB), and rapid eye movement-sleep behavior disorder (RBD). We analyzed common and rare variants from 3 cohorts of European descent: 1084 RBD cases and 2945 controls, 2852 PD cases and 1686 controls, and 2610 DLB cases and 1920 controls. Logistic regression models were used to assess common variants while optimal sequence Kernel association tests were used to assess rare variants, both adjusted for sex, age, and principal components. No variants were associated with any of the synucleinopathies, supporting that common and rare NPC1 variants do not play an important role in alpha synucleinopathies.

Centre d'Études Avancées en Médecine du Sommeil Hôpital du Sacré Coeur de Montréal Montréal Quebec Canada; Department of Neurosciences Université de Montréal Montréal Quebec Canada

Centre d'Études Avancées en Médecine du Sommeil Hôpital du Sacré Coeur de Montréal Montréal Quebec Canada; Department of Psychiatry Université de Montréal Montréal Quebec Canada

Centre d'Études Avancées en Médecine du Sommeil Hôpital du Sacré Coeur de Montréal Montréal Quebec Canada; Department of Psychology Université du Québec à Montréal Montréal Quebec Canada

Department of Biomedical and Neuromotor Sciences Alma Mater Studiorum University of Bologna Bologna Italy

Department of Biomedical Metabolic and Neural Sciences University of Modena and Reggio Emilia Modena Italy; IRCCS Institute of Neurological Sciences of Bologna Bologna Italy

Department of Clinical Neurophysiology and Sleep Center University Lille North of France CHU Lille Lille France

Department of Medical Sciences and Public Health Sleep Disorder Research Center University of Cagliari Cagliari Italy

Department of Neurological Sciences Università Vita Salute San Raffaele Milan Italy

Department of Neurology and Centre of Clinical Neuroscience Charles University 1st Faculty of Medicine and General University Hospital Prague Czech Republic

Department of Neurology Mayo Clinic Rochester MN USA

Department of Neurology Philipps University Marburg Germany

Department of Neurology Sleep Disorders Clinic Medical University of Innsbruck Innsbruck Austria

Department of Neurology Sleep Disorders Clinic Medical University of Innsbruck Innsbruck Austria; Department of Sleep Medicine and Neuromuscular Disorders University of Münster Münster Germany

Department of Neurology University Medical Centre Göttingen Göttingen Germany; Paracelsus Elena Klinik Kassel Germany

Department of Neurosciences Clinical Neurology Unit University Hospital of Udine Udine Italy

Department of Neurosciences Clinical Neurology Unit University Hospital of Udine Udine Italy; Department of Medicine University of Udine Udine Italy

IRCCS Institute of Neurological Sciences of Bologna Bologna Italy; Department of Neurosciences Neurology Unit Movement Disorders Division Biomedicine and Movement Sciences University of Verona Verona Italy

Laboratory for Sleep Disorders St Dimpna Regional Hospital Geel Belgium; Department of Neurology St Dimpna Regional Hospital Geel Belgium

Laboratory for Sleep Disorders St Dimpna Regional Hospital Geel Belgium; Department of Neurology St Dimpna Regional Hospital Geel Belgium; Department of Neurology University Hospital Antwerp Edegem Antwerp Belgium

National Reference Centre for Orphan Diseases Narcolepsy Rare hypersomnias Sleep Unit Department of Neurology CHU Montpellier Institute for Neurosciences of Montpellier INM Univ Montpellier INSERM Montpellier France

Nuffield Department of Clinical Neurosciences University of Oxford Oxford UK

Paracelsus Elena Klinik Kassel Germany; Department of Neurology Philipps University Marburg Germany

Sleep and Neurology Unit Beau Soleil Clinic Montpellier France; EuroMov University of Montpellier Montpellier France

Sleep disorder Unit Carémeau Hospital University Hospital of Nîmes France

Sleep Disorders Unit Sorbonne University Institut du Cerveau Paris Brain Institute ICM Inserm CNRS AP HP Hôpital de la Pitié Salpêtrière Paris France

The Neuro McGill University Montréal Quebec Canada; Department of Human Genetics McGill University Montréal Quebec Canada

The Neuro McGill University Montréal Quebec Canada; Department of Human Genetics McGill University Montréal Quebec Canada; Department of Neurology and Neurosurgery McGill University Montréal Quebec Canada

The Neuro McGill University Montréal Quebec Canada; Department of Neurology and Neurosurgery McGill University Montréal Quebec Canada

The Neuro 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 Coeur de Montréal Montréal Quebec Canada

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