Lack of epistatic interaction of SNCA with APOE in synucleinopathies

Prabhjyot Saini; Eric Yu; Mehrdad A Estiar; Lynne Krohn; Kheireddin Mufti; Uladzislau Rudakou; Jennifer A Ruskey; Farnaz Asayesh; Sandra B Laurent; Dan Spiegelman; Isabelle Arnulf; Jacques Y Montplaisir; Jean-François Gagnon; Alex Desautels; Yves Dauvilliers; Gian Luigi Gigli; Mariarosaria Valente; Francesco Janes; Andrea Bernardini; Karel Šonka; David Kemlink; Wolfgang H Oertel; Karri Kaivola; Annette Janzen; Giuseppe Plazzi; Elena Antelmi; Francesco Biscarini; 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; Victoria Anselmi; Abubaker Ibrahim; Ambra Stefani; Birgit Högl; Michele T M Hu; Sonja W Scholz; Ziv Gan-Or

doi:10.1093/braincomms/fcaf455

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Lack of epistatic interaction of SNCA with APOE in synucleinopathies

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Lack of epistatic interaction of SNCA with APOE in synucleinopathies

Prabhjyot Saini, Eric Yu, Mehrdad A Estiar, Lynne Krohn, Kheireddin Mufti, Uladzislau Rudakou, Jennifer A Ruskey, Farnaz Asayesh, Sandra B Laurent, Dan Spiegelman, …

Brain communications, Vol.7(6), p.fcaf455

17/11/2025

DOI: https://doi.org/10.1093/braincomms/fcaf455

PMID: 41341545

Résumé

dementia with Lewy bodies

epistasis

REM sleep behaviour disorder

synucleinopathies

Parkinson’s disease

Two recent studies suggested that the ε4 haplotype was associated with increased α-synuclein pathology in cell and mouse models. Genetic variants in the region have strong association with Parkinson's disease (PD), dementia with Lewy bodies (DLB) and idiopathic REM sleep behaviour disorder (iRBD), while is a genetic risk determinant for only DLB. To determine if genetic-level interactions between and exists that can explain the protein-level association, we investigated the genotypic interaction of and in cohorts of PD, DLB and iRBD. We analysed genome-wide association study (GWAS) data from 5229 PD patients and 5480 controls, 2610 DLB patients and 1920 controls, and 1055 iRBD patients and 3667 controls. We used logistic regression interaction models across all three cohorts independently between the (i) top GWAS signals of single nucleotide polymorphisms (SNPs) and haplotypes and (ii) SNP×SNP and three-way SNP interaction across the entire coding region plus 200 kb flanking each gene. No significant interactions were found to be associated with any of the synucleinopathies after correction for multiple testing. Our results do not support a role for genetic interactions between and across PD, DLB and iRBD. Since the tested genetic variants affect the expression and function of these proteins, it is likely that any interactions between them do not affect the risk of PD, DLB and iRBD.

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Titre: Lack of epistatic interaction of SNCA with APOE in synucleinopathies
Créateurs - sans rôle: Prabhjyot Saini - McGill University
Eric Yu - McGill University
Mehrdad A Estiar - Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA
Lynne Krohn - Department of Human Genetics, McGill University, Montreal, Quebec, Canada H3A 1Y2
Kheireddin Mufti - McGill University
Uladzislau Rudakou - McGill University
Jennifer A Ruskey - McGill University
Farnaz Asayesh - McGill University
Sandra B Laurent - Centre Hospitalier Universitaire Sainte-Justine
Dan Spiegelman - McGill University
Isabelle Arnulf - Sleep Disorders Unit, Pitié-Salpêtrière Hospital, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, and Sorbonne Universités, Paris 75013, France
Jacques Y Montplaisir - Université de Montréal
Jean-François Gagnon - Department of Psychology, Université du Québec à Montréal, Montreal, Quebec, Canada H2X 3JB
Alex Desautels - Université de Montréal
Yves Dauvilliers - National Reference Center for Narcolepsy, Sleep Unit, Department of Neurology, Gui-de-Chauliac Hospital, Centre Hospitalier Universitaire Montpellier, University of Montpellier, INSERM U1061, Montpellier 34090, France
Gian Luigi Gigli - University of Udine
Mariarosaria Valente - University of Udine
Francesco Janes - Clinical Neurology Unit, Department of Head and Neck, University Hospital of Udine, Udine 33100, Italy
Andrea Bernardini - Clinical Neurology Unit, Department of Head and Neck, University Hospital of Udine, Udine 33100, Italy
Karel Šonka - Charles University
David Kemlink - Charles University
Wolfgang H Oertel - Philipps University of Marburg
Karri Kaivola - Neurodegenerative Diseases Research Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA
Annette Janzen - Department of Neurology, Philipps University Marburg, Marburg 35032, Germany
Giuseppe Plazzi - IRCCS-Institute of Neurological Sciences of Bologna, Bologna 40139, Italy
Elena Antelmi - University of Verona
Francesco Biscarini - University of Bologna
Michela Figorilli - University of Cagliari
Monica Puligheddu - University of Cagliari
Brit Mollenhauer - Department of Neurology, University Medical Center Göttingen, Göttingen 37075, Germany
Claudia Trenkwalder - Department of Neurology, University Medical Center Göttingen, Göttingen 37075, Germany
Friederike Sixel-Döring - Paracelsus Elena Klinik Kassel
Valérie Cochen De Cock - EuroMov Research Laboratory, University of Montpellier, Montpellier 34090, France
Christelle Charley Monaca - Department of Clinical Neurophysiology and Sleep Center, University of Lille Nord de France, Centre Hospitalier Universitaire Lille, Lille 59045, France
Anna Heidbreder - Department of Neurology and Clinical Research Institute for Neuroscience, Johannes Kepler University Linz, Linz 4020, Austria
Luigi Ferini-Strambi - Department of Neurological Sciences, Università Vita-Salute San Raffaele, Milan 20132, Italy
Femke Dijkstra - Department of Neurology, University Hospital Antwerp, Edegem, Antwerp 2650, Belgium
Mineke Viaene - Department of Neurology, Sint-Dimpna Regional Hospital, Geel 2440, Belgium
Beatriz Abril - Sleep Disorder Unit, Carémeau Hospital, Centre Hospitalier Universitaire Nîmes, Nîmes 30029, France
Bradley F Boeve - Mayo Clinic
Ronald B Postuma - McGill University
Guy A Rouleau - Department of Human Genetics, McGill University, Montreal, Quebec, Canada H3A 1Y2
Victoria Anselmi - National Reference Center for Narcolepsy, Sleep Unit, Department of Neurology, Gui-de-Chauliac Hospital, Centre Hospitalier Universitaire Montpellier, University of Montpellier, INSERM U1061, Montpellier 34090, France
Abubaker Ibrahim - Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck 6020, Austria
Ambra Stefani - Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck 6020, Austria
Birgit Högl - Sleep Disorders Clinic, Department of Neurology, Medical University of Innsbruck, Innsbruck 6020, Austria
Michele T M Hu - Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK
Sonja W Scholz - Johns Hopkins University School of Medicine
Ziv Gan-Or - Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada H3A 2B4
Détails de publication: Brain communications, Vol.7(6), p.fcaf455
Identifiants: 99139838709311
Unité académique: Institut des Neurosciences de Montpellier - INM
Langue: English
Type de ressource: Journal article