medRxiv : the preprint server for health sciences · 2026
The GBA1 p.E427K (p.E388K) Variant is a Risk Factor for Synucleinopathies: A Meta-Analysis.
СтатьяПрепринтНазвание и аннотация: Перевод пока не подготовлен
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Chifamba Leah V, Parlar Sitki Cem, Somerville Emma N, Liu Lang, Yu Eric, Asayesh Farnaz, Ahmad Jamil, Teferra Meron, Ruskey Jennifer A, Waters Cheryl, Monchi Oury, Dauvilliers Yves, Dupré Nicolas, Timofeeva Alla, Emelyanov Anton, Pchelina Sofya, Miliukhina Irina, Greenbaum Lior, Hassin-Baer Sharon, Goldstein Orly, Radefeldt Mandy, Bauer Peter, Beetz Christian, Dilliott Allison A, Beck James C, Senkevich Konstantin, ROPAD Study Group, Parkinson’s Foundation PD GENEration Study, Klein Christine, Alcalay Roy N, Gan-Or Ziv
Аннотация
BACKGROUND: Variants in GBA1 are important genetic risk factors for synucleinopathies, including Parkinson's disease (PD). While several GBA1 variants are established risk or severity modifiers, the role of the p.E427K variant remains unclear.
OBJECTIVE: 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 (ORs) were calculated for each cohort and pooled using a random-effects model.
RESULTS: Across 67,484 patients and 124,079 controls, GBA1 p.E427K was associated with increased disease risk (pooled OR = 1.87, 95% CI 1.28-2.72, P = 0.001). 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.
OBJECTIVE: 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 (ORs) were calculated for each cohort and pooled using a random-effects model.
RESULTS: Across 67,484 patients and 124,079 controls, GBA1 p.E427K was associated with increased disease risk (pooled OR = 1.87, 95% CI 1.28-2.72, P = 0.001). 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.