Synucleinopathies-related disorders such as Lewy body dementia (LBD) and isolated/idiopathic REM sleep behavior disorder (iRBD) have been associated with neuroinflammation. In this study, we examined whether the human leukocyte antigen (HLA) locus plays a role in iRBD and LBD. In iRBD, HLA-DRB1*11:01 was the only allele passing FDR correction (OR = 1.57, 95% CI = 1.27-1.93, p = 2.70e-05). We also discovered associations between iRBD and HLA-DRB1 70D (OR = 1.26, 95%CI = 1.12-1.41, p = 8.76e-05), 70Q (OR = 0.81, 95%CI = 0.72-0.91, p = 3.65e-04) and 71R (OR = 1.21, 95%CI = 1.08-1.35, p = 1.35e-03). Position 71 (pomnibus = 0.00102) and 70 (pomnibus = 0.00125) were associated with iRBD. Our results suggest that the HLA locus may have different roles across synucleinopathies.

Center for Advanced Research in Sleep Medicine Centre Intégré Universitaire de Santé et de Services Sociaux du Nord de l'Île de Montréal Hôpital du Sacré Coeur de Montréal Montréal Québec Canada

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

Department for Sleep Medicine and Neuromuscular disease University Hospital Muenster Muenster Germany

Department of Biomedical Metabolic and Neural Sciences University of Modena and Reggio Emilia Modena Italy

Department of Human Genetics McGill University Montréal Québec Canada

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

Department of Medicine University of Udine Udine 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 and Neurosurgery McGill University Montréal Québec Canada

Department of Neurology Johns Hopkins University Medical Center Baltimore Maryland USA

Department of Neurology Mayo Clinic Rochester Minnesota USA

Department of Neurology Philipps University Marburg Germany

Department of Neurology St Dimpna Regional Hospital Geel Belgium

Department of Neurology University Hospital Antwerp Edegem Antwerp Belgium

Department of Neurosciences Université de Montréal Montréal Québec Canada

Department of Neurosurgery University Medical Centre Göttingen Göttingen Germany

Department of Psychiatry Université de Montréal Montréal Québec Canada

Department of Psychology Université du Québec à Montréal Montréal Québec Canada

Division of Neurology Nuffield Department of Clinical Neurosciences University of Oxford Oxford UK

EuroMov Digital Health in Motion University of Montpellier IMT Mines Ales Montpellier France

IRCCS Institute of Neurological Sciences of Bologna Bologna Italy

Laboratory for Sleep Disorders St Dimpna Regional Hospital Geel Belgium

National Reference Center for Narcolepsy Sleep Unit Department of Neurology Gui de Chauliac Hospital CHU Montpellier University of Montpellier Inserm U1061 Montpellier France

Neurodegenerative Diseases Research Unit National Institute of Neurological Disorders and Stroke Bethesda Maryland USA

Neurology Unit Movement Disorders Division Department of Neurosciences Biomedicine and Movement Sciences University of Verona Verona Italy

Neuromuscular Diseases Research Section National Institute on Aging Bethesda Maryland USA

Oxford Parkinson's Disease Centre University of Oxford Oxford UK

Paracelsus Elena Klinik Kassel Germany

Sleep and Neurology Unit Beau Soleil Clinic Montpellier France

Sleep disorder Unit Carémeau Hospital University Hospital of Nîmes Nîmes France

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

Sleep Disorders Unit Pitié Salpêtrière Hospital Paris Brain Institute and Sorbonne University Paris France

The Neuro McGill University Montréal Québec Canada

medRxiv. 2023 Apr 03:2023.01.31.23284682. doi: 10.1101/2023.01.31.23284682. PubMed

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