Impact of GBA1 variants on long-term clinical progression and mortality in incident Parkinson’s disease
Creators: name: Stoker, Thomas B
name: Camacho, Marta
name: Winder-Rhodes, Sophie
name: Liu, Ganqiang
name: Scherzer, Clemens R
name: Foltynie, Thomas
name: Evans, Jonathan
name: Breen, David P
name: Barker, Roger A
name: Williams-Gray, Caroline H
Publisher: name: Apollo - University of Cambridge Repository
Year: 2020
Subjects: Movement disorders
1506

description: Funder: Foundation for the National Institutes of Health; FundRef: http://dx.doi.org/10.13039/100000009
description: Funder: Van Geest Foundation
description: Funder: Patrick Berthoud Charitable Trust; FundRef: http://dx.doi.org/10.13039/501100004218
description: Funder: Cure Parkinson's Trust
description: Funder: Michael J Fox Foundation
description: Funder: Innovate UK; FundRef: http://dx.doi.org/10.13039/501100006041
description: Funder: Dooley LLC
description: Funder: American Parkinson's disease association
description: Funder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265
description: Funder: Cambridge Centre for Parkinson-Plus
description: Funder: Parkinson's UK; FundRef: http://dx.doi.org/10.13039/501100000304
description: Funder: John Black charitable foundation
description: Funder: Wellcome Trust; FundRef: http://dx.doi.org/10.13039/100004440
description: Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272
description: Funder: Van Andel Research Institute; FundRef: http://dx.doi.org/10.13039/100006019
description: Introduction: Variants in the GBA1 gene have been identified as a common risk factor for Parkinson’s disease (PD). In addition to pathogenic mutations (those associated with Gaucher disease), a number of ‘non-pathogenic’ variants also occur at increased frequency in PD. Previous studies have reported that pathogenic variants adversely affect the clinical course of PD. The role of ‘non-pathogenic’ GBA1 variants on PD course is less clear. In this study, we report the effect of GBA1 variants in incident PD patients with long-term follow-up. Methods: The study population consisted of patients in the Cambridgeshire Incidence of Parkinson’s disease from General Practice to Neurologist and Parkinsonism: Incidence, Cognition and Non-motor heterogeneity in Cambridgeshire cohorts. Patients were grouped into non-carriers, carriers of ‘non-pathogenic’ GBA1 variants and carriers of pathogenic GBA1 mutations. Survival analyses for time to development of dementia, postural instability and death were carried out. Cox regression analysis controlling for potential confounders were used to determine the impact of GBA1 variants on these outcome measures. Results: GBA1 variants were identified in 14.4% of patients. Pathogenic and ‘non-pathogenic’ GBA1 variants were associated with the accelerated development of dementia and a more aggressive motor course. Pathogenic GBA1 variants were associated with earlier mortality in comparison with non-carriers, independent of the development of dementia. Discussion: GBA1 variants, including those not associated with Gaucher disease, are common in PD and result in a more aggressive disease course.