The GBA1 p. E427K (p. E388K ) Variant Is a Risk Factor for Synucleinopathies: A Meta‐Analysis
Year: 2026
Type: article
Study designs: Systematic Review, Meta-Analysis
Abstract: BACKGROUND: Variants in GBA1 are important genetic risk factors for synucleinopathies, including Parkinson's disease (PD). Although several GBA1 variants are established risk or severity modifiers, the role of the p.E427K variant remains unclear. OBJECTIVE: The aim was to determine whether the GBA1 p.E427K variant is associated with risk of synucleinopathies. METHODS: We performed a meta-analysis of case-control studies reporting the frequency of GBA1 p.E427K (p.E388K) in PD and related synucleinopathies. Data were obtained from published studies, open-access resources, and large cohorts, including in-house datasets. Odds ratios (OR) were calculated for each cohort and pooled using a random-effects model. RESULTS: Across 67,221 patients and 123,832 controls, GBA1 p.E427K was associated with increased disease risk (pooled OR = 1.94, 95% confidence interval 1.33-2.84, P = 0.0007). Enzymatic data showed reduced glucocerebrosidase activity in carriers. CONCLUSIONS: The GBA1 p.E427K variant is a risk factor for synucleinopathies and should be considered in genetic studies and clinical trials. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Source: Movement Disorders
DOI: 10.1002/mds.70367
Authors: Leah V. Chifamba, Sitki Cem Parlar, Emma N. Somerville, Lang Liu, Eric Yu, Farnaz Asayesh, Jamil Ahmad, Meron Teferra, Jennifer A. Ruskey, Cheryl Waters, Oury Monchi, Yves Dauvilliers, Nicolas Dupré, Alla Timofeeva, Anton Emelyanov, Sofya Pchelina, Irina Miliukhina, Lior Greenbaum, Sharon Hassin‐Baer, Orly Goldstein, Mandy Radefeldt, Peter Bauer, Christian Beetz, Allison A. Dilliott, James C. Beck, Konstantin Senkevich, ROPAD Study Group, Christine Klein, Roy N. Alcalay, Ziv Gan‐Or
Institutions: Montreal Neurological Institute and Hospital, McGill University, Columbia University Irving Medical Center, Institut Universitaire de Gériatrie de Montréal, Université de Montréal, Université de Montpellier, Centre Hospitalier Universitaire de Montpellier, Hôpital Gui de Chauliac, Université Laval, CHU de Québec-Université Laval, First Pavlov State Medical University of St. Petersburg, Russian Academy of Sciences, Institute of the Human Brain, Tel Aviv University, Sheba Medical Center, Tel Aviv Sourasky Medical Center, Centogene (Germany), Parkinson's Foundation, McGill University Health Centre, University Hospital Schleswig-Holstein, University of Lübeck
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,480
Funders: Michael J. Fox Foundation for Parkinson's Research, Brookdale Foundation Group, McGill University, Compute Canada, Parkinson's Foundation, Consortium canadien en neurodégénérescence associée au vieillissement, Canada First Research Excellence Fund, National Institutes of Health, National Institute of Neurological Disorders and Stroke
OpenAlex ID: W7162189942