Movement DisordersGenetic & Genomic MedicinePeer-reviewed journal article
The GBA1 p.E427K (p.E388K) Variant is a Risk Factor for Synucleinopathies: A Meta-Analysis
Leah V. ChifambaiD, Sitki Cem ParlariD, Emma N. SomervilleiD, Lang LiuiD, Eric YuiD, Farnaz AsayeshiD, Jamil Ahmad, Meron TeferraiD, Jennifer A. RuskeyiD, Cheryl WatersiD, Oury MonchiiD, Yves A DauvilliersiD, Nicolas DupréiD, Alla TimofeevaiD, Anton EmelyanoviD, Sofya PchelinaiD, Irina V. MiliukhinaiD, Lior GreenbaumiD, Sharon Hassin‐BaeriD, Orly GoldsteiniD, Mandy Radefeldt, Peter BaueriD, Christian BeetziD, Allison Ann DilliottiD, James C. BeckiD, , Ziv Gan‐OriD
Abstract
BackgroundVariants in GBA1 are important genetic risk factors for synucleinopathies, including Parkinsons 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. MethodsWe 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. ResultsAcross 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. ConclusionsThe GBA1 p.E427K variant is a risk factor for synucleinopathies and should be considered in genetic studies and clinical trials.
- organism: human
- assay: GWAS summary statistics
- research focus: GWAS / association mapping
- approach: statistical model
- Citations
- 0
- FWCI
- 0.00
- Field percentile
- 35th percentile
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