PMID- 36778313
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240216
DP  - 2023 Apr 3
TI  - HLA in isolated REM sleep behavior disorder and Lewy body dementia.
LID - 2023.01.31.23284682 [pii]
LID - 10.1101/2023.01.31.23284682 [doi]
AB  - BACKGROUND AND OBJECTIVES: Isolated/idiopathic REM sleep behavior disorder (iRBD) 
      and Lewy body dementia (LBD) are synucleinopathies that have partial genetic 
      overlap with Parkinson's disease (PD). Previous studies have shown that 
      neuroinflammation plays a substantial role in these disorders. In PD, specific 
      residues of the human leukocyte antigen ( HLA ) were suggested to be associated 
      with a protective effect. This study examined whether the HLA locus plays a 
      similar role in iRBD, LBD and PD. METHODS: We performed HLA imputation on iRBD 
      genotyping data (1,072 patients and 9,505 controls) and LBD whole-genome 
      sequencing (2,604 patients and 4,032 controls) using the multi-ethnic HLA 
      reference panel v2 from the Michigan Imputation Server. Using logistic 
      regression, we tested the association of HLA alleles, amino acids and haplotypes 
      with disease susceptibility. We included age, sex and the top 10 principal 
      components as covariates. We also performed an omnibus test to examine which HLA 
      residue positions explain the most variance. RESULTS: 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). In HLA-DRB1 , 
      position 71 ( p (omnibus) =0.00102) and 70 ( p (omnibus) =0.00125) were 
      associated with iRBD. We found no association in LBD. DISCUSSION: This study 
      identified an association between HLA-DRB1 11:01 and iRBD, distinct from the 
      previously reported association in PD. Therefore, the HLA locus may play 
      different roles across synucleinopathies. Additional studies are required better 
      to understand HLA's role in iRBD and LBD.
FAU - Yu, Eric
AU  - Yu E
AD  - Department of Human Genetics, McGill University, Montreal, QC, Canada.
AD  - The Neuro (Montreal Neurological Institute-Hospital), McGill University, 
      Montreal, QC, Canada.
FAU - Krohn, Lynne
AU  - Krohn L
AD  - Department of Human Genetics, McGill University, Montreal, QC, Canada.
AD  - The Neuro (Montreal Neurological Institute-Hospital), McGill University, 
      Montreal, QC, Canada.
FAU - Ruskey, Jennifer A
AU  - Ruskey JA
AD  - The Neuro (Montreal Neurological Institute-Hospital), McGill University, 
      Montreal, QC, Canada.
AD  - Department of Neurology and Neurosurgery, McGill University, Montreal, QC, 
      Canada.
FAU - Asayesh, Farnaz
AU  - Asayesh F
AD  - The Neuro (Montreal Neurological Institute-Hospital), McGill University, 
      Montreal, QC, Canada.
AD  - Department of Neurology and Neurosurgery, McGill University, Montreal, QC, 
      Canada.
FAU - Spiegelman, Dan
AU  - Spiegelman D
AD  - The Neuro (Montreal Neurological Institute-Hospital), McGill University, 
      Montreal, QC, Canada.
AD  - Department of Neurology and Neurosurgery, McGill University, Montreal, QC, 
      Canada.
FAU - Shah, Zalak
AU  - Shah Z
AD  - Neurodegenerative Diseases Research Unit, National Institute of Neurological 
      Disorders and Stroke, Bethesda, MD, USA.
FAU - Chia, Ruth
AU  - Chia R
AD  - Neuromuscular Diseases Research Section, National Institute on Aging, Bethesda, 
      MD, USA.
FAU - Arnulf, Isabelle
AU  - Arnulf I
AD  - Sleep Disorders Unit, Pitie Salpetriere Hospital, Paris Brain Institute and 
      Sorbonne University, Paris, France.
FAU - Hu, Michele T M
AU  - Hu MTM
AD  - Oxford Parkinson's Disease Centre (OPDC), University of Oxford, Oxford, United 
      Kingdom.
AD  - Division of Neurology, Nuffield Department of Clinical Neurosciences, University 
      of Oxford, Oxford, United Kingdom.
FAU - Montplaisir, Jacques Y
AU  - Montplaisir JY
AD  - Center for Advanced Research in Sleep Medicine, Centre Integre Universitaire de 
      Sante et de Services Sociaux du Nord-de-l'ile-de-Montreal - Hopital du 
      Sacre-Coeur de Montreal, Montreal, QC, Canada.
AD  - Department of Psychiatry, Universite de Montreal, Montreal, QC, Canada.
FAU - Gagnon, Jean-Francois
AU  - Gagnon JF
AD  - Center for Advanced Research in Sleep Medicine, Centre Integre Universitaire de 
      Sante et de Services Sociaux du Nord-de-l'ile-de-Montreal - Hopital du 
      Sacre-Coeur de Montreal, Montreal, QC, Canada.
AD  - Department of Psychology, Universite du Quebec a Montreal, Montreal, QC, Canada.
FAU - Desautels, Alex
AU  - Desautels A
AD  - Center for Advanced Research in Sleep Medicine, Centre Integre Universitaire de 
      Sante et de Services Sociaux du Nord-de-l'ile-de-Montreal - Hopital du 
      Sacre-Coeur de Montreal, Montreal, QC, Canada.
AD  - Department of Neurosciences, Universite de Montreal, Montreal, QC, Canada.
FAU - Dauvilliers, Yves
AU  - Dauvilliers Y
AD  - National Reference Center for Narcolepsy, Sleep Unit, Department of Neurology, 
      Gui-de-Chauliac Hospital, CHU Montpellier, University of Montpellier, Inserm 
      U1061, Montpellier, France.
FAU - Gigli, Gian Luigi
AU  - Gigli GL
AD  - Clinical Neurology Unit, Department of Neurosciences, University Hospital of 
      Udine, Udine, Italy.
AD  - Department of Medicine (DAME), University of Udine, Udine, Italy.
FAU - Valente, Mariarosaria
AU  - Valente M
AD  - Clinical Neurology Unit, Department of Neurosciences, University Hospital of 
      Udine, Udine, Italy.
AD  - Department of Medicine (DAME), University of Udine, Udine, Italy.
FAU - Janes, Francesco
AU  - Janes F
AD  - Clinical Neurology Unit, Department of Neurosciences, University Hospital of 
      Udine, Udine, Italy.
FAU - Bernardini, Andrea
AU  - Bernardini A
AD  - Clinical Neurology Unit, Department of Neurosciences, University Hospital of 
      Udine, Udine, Italy.
FAU - Hogl, Birgit
AU  - Hogl B
AD  - Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, 
      Innsbruck, Austria.
FAU - Stefani, Ambra
AU  - Stefani A
AD  - Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, 
      Innsbruck, Austria.
FAU - Ibrahim, Abubaker
AU  - Ibrahim A
AD  - Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, 
      Innsbruck, Austria.
FAU - Heidbreder, Anna
AU  - Heidbreder A
AD  - Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, 
      Innsbruck, Austria.
AD  - Department for Sleep Medicine and Neuromuscular disease, University Hospital 
      Muenster, Muenster, Germany.
FAU - Sonka, Karel
AU  - Sonka K
AD  - Department of Neurology and Centre of Clinical Neuroscience, Charles University, 
      First Faculty of Medicine and General University Hospital, Prague, Czech 
      Republic.
FAU - Dusek, Petr
AU  - Dusek P
AD  - Department of Neurology and Centre of Clinical Neuroscience, Charles University, 
      First Faculty of Medicine and General University Hospital, Prague, Czech 
      Republic.
FAU - Kemlink, David
AU  - Kemlink D
AD  - Department of Neurology and Centre of Clinical Neuroscience, Charles University, 
      First Faculty of Medicine and General University Hospital, Prague, Czech 
      Republic.
FAU - Oertel, Wolfgang
AU  - Oertel W
AD  - Department of Neurology, Philipps University, Marburg, Germany.
FAU - Janzen, Annette
AU  - Janzen A
AD  - Department of Neurology, Philipps University, Marburg, Germany.
FAU - Plazzi, Giuseppe
AU  - Plazzi G
AD  - Department of Biomedical, Metabolic and Neural Sciences, University of Modena and 
      Reggio-Emilia, Modena, Italy.
AD  - IRCCS, Institute of Neurological Sciences of Bologna, Bologna, Italy.
FAU - Antelmi, Elena
AU  - Antelmi E
AD  - Neurology Unit, Movement Disorders Division, Department of Neurosciences, 
      Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
FAU - Figorilli, Michela
AU  - Figorilli M
AD  - Department of Medical Sciences and Public Health, Sleep Disorder Research Center, 
      University of Cagliari, Cagliari, Italy.
FAU - Puligheddu, Monica
AU  - Puligheddu M
AD  - Department of Medical Sciences and Public Health, Sleep Disorder Research Center, 
      University of Cagliari, Cagliari, Italy.
FAU - Mollenhauer, Brit
AU  - Mollenhauer B
AD  - Paracelsus-Elena-Klinik, Kassel, Germany.
AD  - Department of Neurosurgery, University Medical Centre Gaettingen, Gottingen, 
      Germany.
FAU - Trenkwalder, Claudia
AU  - Trenkwalder C
AD  - Paracelsus-Elena-Klinik, Kassel, Germany.
AD  - Department of Neurosurgery, University Medical Centre Gaettingen, Gottingen, 
      Germany.
FAU - Sixel-Doring, Friederike
AU  - Sixel-Doring F
AD  - Department of Neurology, Philipps University, Marburg, Germany.
AD  - Paracelsus-Elena-Klinik, Kassel, Germany.
FAU - De Cock, Valerie Cochen
AU  - De Cock VC
AD  - Sleep and Neurology Unit, Beau Soleil Clinic, Montpellier, France.
AD  - EuroMov Digital Health in Motion, University of Montpellier IMT Mines Ales, 
      Montpellier, France.
FAU - Ferini-Strambi, Luigi
AU  - Ferini-Strambi L
AD  - Department of Neurological Sciences, Universita Vita-Salute San Raffaele, Milan, 
      Italy.
FAU - Dijkstra, Femke
AU  - Dijkstra F
AD  - Laboratory for Sleep Disorders, St. Dimpna Regional Hospital, Geel, Belgium.
AD  - Department of Neurology, St. Dimpna Regional Hospital, Geel, Belgium.
AD  - Department of Neurology, University Hospital Antwerp, Edegem, Antwerp, Belgium.
FAU - Viaene, Mineke
AU  - Viaene M
AD  - Laboratory for Sleep Disorders, St. Dimpna Regional Hospital, Geel, Belgium.
AD  - Department of Neurology, St. Dimpna Regional Hospital, Geel, Belgium.
FAU - Abril, Beatriz
AU  - Abril B
AD  - Sleep disorder Unit, Caremeau Hospital, University Hospital of Nimes, France.
FAU - Boeve, Bradley F
AU  - Boeve BF
AD  - Department of Neurology, Mayo Clinic, Rochester, MN, USA.
FAU - Rouleau, Guy A
AU  - Rouleau GA
AD  - Department of Human Genetics, McGill University, Montreal, QC, Canada.
AD  - The Neuro (Montreal Neurological Institute-Hospital), McGill University, 
      Montreal, QC, Canada.
AD  - Department of Neurology and Neurosurgery, McGill University, Montreal, QC, 
      Canada.
FAU - Postuma, Ronald B
AU  - Postuma RB
AD  - The Neuro (Montreal Neurological Institute-Hospital), McGill University, 
      Montreal, QC, Canada.
AD  - Department of Neurology and Neurosurgery, McGill University, Montreal, QC, 
      Canada.
AD  - Center for Advanced Research in Sleep Medicine, Centre Integre Universitaire de 
      Sante et de Services Sociaux du Nord-de-l'ile-de-Montreal - Hopital du 
      Sacre-Coeur de Montreal, Montreal, QC, Canada.
FAU - Scholz, Sonja W
AU  - Scholz SW
AD  - Neurodegenerative Diseases Research Unit, National Institute of Neurological 
      Disorders and Stroke, Bethesda, MD, USA.
AD  - Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, 
      USA.
CN  - International LBD Genomics Consortium
FAU - Gan-Or, Ziv
AU  - Gan-Or Z
AD  - Department of Human Genetics, McGill University, Montreal, QC, Canada.
AD  - The Neuro (Montreal Neurological Institute-Hospital), McGill University, 
      Montreal, QC, Canada.
AD  - Department of Neurology and Neurosurgery, McGill University, Montreal, QC, 
      Canada.
LA  - eng
GR  - ZIA NS003154/ImNIH/Intramural NIH HHS/United States
PT  - Preprint
DEP - 20230403
PL  - United States
TA  - medRxiv
JT  - medRxiv : the preprint server for health sciences
JID - 101767986
UIN - Ann Clin Transl Neurol. 2023 Jul 4;:. PMID: 37401389
PMC - PMC9915822
EDAT- 2023/02/14 06:00
MHDA- 2023/02/14 06:01
PMCR- 2023/04/07
CRDT- 2023/02/13 03:46
PHST- 2023/02/14 06:00 [pubmed]
PHST- 2023/02/14 06:01 [medline]
PHST- 2023/02/13 03:46 [entrez]
PHST- 2023/04/07 00:00 [pmc-release]
AID - 2023.01.31.23284682 [pii]
AID - 10.1101/2023.01.31.23284682 [doi]
PST - epublish
SO  - medRxiv [Preprint]. 2023 Apr 3:2023.01.31.23284682. doi: 
      10.1101/2023.01.31.23284682.