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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

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
Karl Heilbron
  • Fonction : Auteur
Femke Dijkstra
Mineke Viaene
Paul Cannon
  • Fonction : Auteur
Nicolas Dupré


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.

Dates et versions

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



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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