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Article Dans Une Revue Annals of Neurology Année : 2020

Fine‐Mapping of SNCA in Rapid Eye Movement Sleep Behavior Disorder and Overt Synucleinopathies

Lynne Krohn (1, 2) , Richard Wu (1, 3) , Karl Heilbron (4) , Jennifer Ruskey (2) , Sandra Laurent (2) , Cornelis Blauwendraat (5) , Armaghan Alam (6, 2) , Isabelle Arnulf (7) , Michele Hu (8, 9) , Yves Dauvilliers (10) , Birgit Högl (11) , Mathias Toft (12) , Kari Anne Bjørnarå (12) , Ambra Stefani (11) , Evi Holzknecht (11) , Christelle Charley Monaca (13) , Beatriz Abril (14) , Giuseppe Plazzi (15, 16) , Elena Antelmi (15, 17) , Luigi Ferini-Strambi (18) , Peter Young (19) , Anna Heidbreder (19) , Valérie Cochen de Cock (20, 21) , Brit Mollenhauer (22, 23) , Friederike Sixel-Döring (22, 23) , Claudia Trenkwalder (22, 23) , Karel Sonka (24) , David Kemlink (24) , Michela Figorilli (25) , Monica Puligheddu (25) , Femke Dijkstra (26) , Mineke Viaene (26) , Wolfang Oertel (27) , Marco Toffoli (28, 29) , Gian Luigi Gigli (30) , Mariarosaria Valente (28) , Jean-François Gagnon (31, 32) , Mike Nalls (33) , Andrew Singleton (5) , Alex Desautels (34, 32) , Jacques Montplaisir (34, 32) , Paul Cannon (4) , Owen Ross (35) , Bradley Boeve (36) , Nicolas Dupré (37) , Edward Fon (2) , Ronald Postuma (2, 34) , Lasse Pihlstrøm (12) , Guy Rouleau (1, 2) , Ziv Gan-Or (1, 2)
1 MUHC - McGill University Health Center [Montreal]
2 Montreal Neurological Institute and Hospital
3 Imperial College London
4 23andMe Inc.
5 NIA - National Institute on Aging [Bethesda, USA]
6 McGill University = Université McGill [Montréal, Canada]
7 CIC Neurosciences - Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière]
8 University of Oxford
9 Nuffield Department of Clinical Neurosciences [Oxford]
10 Département de neurologie [Montpellier]
11 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
12 Oslo University Hospital [Oslo]
13 CHRU Lille - Service de neurophysiologie clinique
14 CHU Nîmes - Hôpital Universitaire Carémeau [Nîmes]
15 UNIBO - Alma Mater Studiorum University of Bologna
16 University of Bologna/Università di Bologna
17 Department of Biomedical and Neuromotor Sciences [Bologna, Italy]
18 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
19 WWU - Westfälische Wilhelms-Universität Münster = University of Münster
20 Clinique Beau Soleil [Montpellier]
21 EuroMov - Euromov
22 Paracelsus-Elena-Klinik, Kassel, Germany.
23 UMG - University Medical Center Göttingen
24 First Faculty of Medicine Charles University [Prague]
25 UniCa - Università degli Studi di Cagliari = University of Cagliari
26 Algemeen Ziekenhuis Sint-Dimpna
27 Philipps Universität Marburg = Philipps University of Marburg
28 Università degli Studi di Udine - University of Udine [Italie]
29 UCL - University College of London [London]
30 Department of Mathematics and Computer Science [Udine]
31 Hôpital du Sacré-Coeur de Montréal
32 UQAM - Université du Québec à Montréal = University of Québec in Montréal
33 Data Tecnica International
34 CEAMS - Centre d'études avancées en Médecine du Sommeil
35 Mayo Clinic [Jacksonville]
36 Mayo Clinic [Rochester]
37 Laval University Medical center
Lynne Krohn
McGill University Health Center [Montreal]
Montreal Neurological Institute and Hospital
Richard Wu
McGill University Health Center [Montreal]
Imperial College London
Karl Heilbron
  • Fonction : Auteur
23andMe Inc.
Jennifer Ruskey
  • Fonction : Auteur
Montreal Neurological Institute and Hospital
Sandra Laurent
  • Fonction : Auteur
Montreal Neurological Institute and Hospital
Cornelis Blauwendraat
  • Fonction : Auteur
National Institute on Aging [Bethesda, USA]
Armaghan Alam
  • Fonction : Auteur
McGill University = Université McGill [Montréal, Canada]
Montreal Neurological Institute and Hospital
Isabelle Arnulf
Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière]
Michele Hu
  • Fonction : Auteur
University of Oxford
Nuffield Department of Clinical Neurosciences [Oxford]
Yves Dauvilliers
Département de neurologie [Montpellier]
Birgit Högl
  • Fonction : Auteur
Innsbruck Medical University = Medizinische Universität Innsbruck
Mathias Toft
  • Fonction : Auteur
Oslo University Hospital [Oslo]
Kari Anne Bjørnarå
  • Fonction : Auteur
Oslo University Hospital [Oslo]
Ambra Stefani
Innsbruck Medical University = Medizinische Universität Innsbruck
Evi Holzknecht
  • Fonction : Auteur
Innsbruck Medical University = Medizinische Universität Innsbruck
Christelle Charley Monaca
  • Fonction : Auteur
Service de neurophysiologie clinique
Beatriz Abril
  • Fonction : Auteur
Hôpital Universitaire Carémeau [Nîmes]
Giuseppe Plazzi
Alma Mater Studiorum University of Bologna
University of Bologna/Università di Bologna
Elena Antelmi
Alma Mater Studiorum University of Bologna
Department of Biomedical and Neuromotor Sciences [Bologna, Italy]
Luigi Ferini-Strambi
Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
Peter Young
  • Fonction : Auteur
Westfälische Wilhelms-Universität Münster = University of Münster
Anna Heidbreder
Westfälische Wilhelms-Universität Münster = University of Münster
Valérie Cochen de Cock
Clinique Beau Soleil [Montpellier]
Euromov
Brit Mollenhauer
Paracelsus-Elena-Klinik, Kassel, Germany.
University Medical Center Göttingen
Friederike Sixel-Döring
  • Fonction : Auteur
Paracelsus-Elena-Klinik, Kassel, Germany.
University Medical Center Göttingen
Claudia Trenkwalder
  • Fonction : Auteur
Paracelsus-Elena-Klinik, Kassel, Germany.
University Medical Center Göttingen
Karel Sonka
First Faculty of Medicine Charles University [Prague]
David Kemlink
First Faculty of Medicine Charles University [Prague]
Michela Figorilli
Università degli Studi di Cagliari = University of Cagliari
Monica Puligheddu
Università degli Studi di Cagliari = University of Cagliari
Femke Dijkstra
Algemeen Ziekenhuis Sint-Dimpna
Mineke Viaene
Algemeen Ziekenhuis Sint-Dimpna
Wolfang Oertel
  • Fonction : Auteur
Philipps Universität Marburg = Philipps University of Marburg
Marco Toffoli
Università degli Studi di Udine - University of Udine [Italie]
University College of London [London]
Gian Luigi Gigli
Department of Mathematics and Computer Science [Udine]
Mariarosaria Valente
Università degli Studi di Udine - University of Udine [Italie]
Jean-François Gagnon
  • Fonction : Auteur
Hôpital du Sacré-Coeur de Montréal
Université du Québec à Montréal = University of Québec in Montréal
Mike Nalls
  • Fonction : Auteur
Data Tecnica International
Andrew Singleton
  • Fonction : Auteur
National Institute on Aging [Bethesda, USA]
Alex Desautels
Centre d'études avancées en Médecine du Sommeil
Université du Québec à Montréal = University of Québec in Montréal
Jacques Montplaisir
  • Fonction : Auteur
Centre d'études avancées en Médecine du Sommeil
Université du Québec à Montréal = University of Québec in Montréal
Paul Cannon
  • Fonction : Auteur
23andMe Inc.
Owen Ross
  • Fonction : Auteur
Mayo Clinic [Jacksonville]
Bradley Boeve
  • Fonction : Auteur
Mayo Clinic [Rochester]
Nicolas Dupré
Laval University Medical center
Edward Fon
  • Fonction : Auteur
Montreal Neurological Institute and Hospital
Ronald Postuma
  • Fonction : Auteur
Montreal Neurological Institute and Hospital
Centre d'études avancées en Médecine du Sommeil
Lasse Pihlstrøm
  • Fonction : Auteur
Oslo University Hospital [Oslo]
Guy Rouleau
McGill University Health Center [Montreal]
Montreal Neurological Institute and Hospital
Ziv Gan-Or
McGill University Health Center [Montreal]
Montreal Neurological Institute and Hospital

Résumé

Rapid eye movement sleep behavior disorder (RBD) is a prodromal synucleinopathy, as >80% will eventually convert to overt synucleinopathy. We performed an in-depth analysis of the SNCA locus to identify RBD-specific risk variants. Methods: Full sequencing and genotyping of SNCA was performed in isolated/idiopathic RBD (iRBD, n = 1,076), Parkinson disease (PD, n = 1,013), dementia with Lewy bodies (DLB, n = 415), and control subjects (n = 6,155). The iRBD cases were diagnosed with RBD prior to neurodegeneration, although some have since converted. A replication cohort from 23andMe of PD patients with probable RBD (pRBD) was also analyzed (n = 1,782 cases; n = 131,250 controls). Adjusted logistic regression models and meta-analyses were performed. Effects on conversion rate were analyzed in 432 RBD patients with available data using Kaplan-Meier survival analysis.Results: A 5'-region SNCA variant (rs10005233) was associated with iRBD (odds ratio [OR] = 1.43, p = 1.1E-08), which was replicated in pRBD. This variant is in linkage disequilibrium (LD) with other 5' risk variants across the different synucleinopathies. An independent iRBD-specific suggestive association (rs11732740) was detected at the 3' of SNCA (OR = 1.32, p = 4.7E-04, not statistically significant after Bonferroni correction). Homozygous carriers of both iRBD-specific SNPs were at highly increased risk for iRBD (OR = 5.74, p = 2E-06). The known top PD-associated variant (3' variant rs356182) had an opposite direction of effect in iRBD compared to PD.

Domaines

Neurosciences Génétique humaine

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https://hal.umontpellier.fr/hal-03481669

Soumis le : mercredi 15 décembre 2021-14:25:48

Dernière modification le : mercredi 21 juin 2023-12:24:04

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Dates et versions

hal-03481669 , version 1 (15-12-2021)

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Citer

Lynne Krohn, Richard Wu, Karl Heilbron, Jennifer Ruskey, Sandra Laurent, et al.. Fine‐Mapping of SNCA in Rapid Eye Movement Sleep Behavior Disorder and Overt Synucleinopathies. Annals of Neurology, 2020, 87 (4), pp.584-598. ⟨10.1002/ana.25687⟩. ⟨hal-03481669⟩

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