GBA1 variants and mortality in Parkinson's disease: A systematic review and meta-analysis.
GBA1 variants are associated with higher all-cause mortality risk in Parkinson's disease
GBA1 variants and mortality in Parkinson's disease: A systematic review and meta-analysis.
Variants in the GBA1 gene are a common genetic risk factor for Parkinson's disease (PD).
This systematic review and meta-analysis synthesizes longitudinal evidence of GBA1 variants as a prognostic factor for all-cause mortality in PD.
We searched MEDLINE, Embase, Cochrane (CENTRAL), ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform for studies comparing mortality in GBA1 -PD versus non-carriers from inception to September 2025.
GBA1 variants raise the risk of dying from any cause
A subgroup analysis suggested a possible severity-dependent effect, with severe variants showing higher point estimates (HR 1.87; 95% CI 1.24-2.82) than mild variants (HR 1.38; 95% CI 1.03-1.83), although the test for subgroup differences was not statistically significant.
GBA1 variants are a significant prognostic marker for reduced survival in PD. This risk may increase with variant severity and persist after adjustment for dementia in the studies that examined this, although the available data is limited.
Limitations include heterogeneous screening methods and predominance of European ancestry in study populations. GBA1 status should be considered a significant prognostic factor for stratification in clinical trials and management.