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<i>GBA1</i> variants and mortality in Parkinson's disease: A systematic review and meta-analysis
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DOI：10.1177/1877718x261470604.png)
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Abstract
En 中文
<jats:sec>
<jats:title>Background</jats:title>
<jats:p>
Variants in the
<jats:italic toggle="yes">GBA1</jats:italic>
gene are a common genetic risk factor for Parkinson's disease (PD). While
<jats:italic toggle="yes">GBA1</jats:italic>
-PD is associated with more rapid motor and cognitive decline, evidence regarding impact on survival remains debatable.
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Objectives</jats:title>
<jats:p>
This systematic review and meta-analysis synthesizes longitudinal evidence of
<jats:italic toggle="yes">GBA1</jats:italic>
variants as a prognostic factor for all-cause mortality in PD.
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods</jats:title>
<jats:p>
We searched MEDLINE, Embase, Cochrane (CENTRAL), ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform for studies comparing mortality in
<jats:italic toggle="yes">GBA1</jats:italic>
-PD versus non-carriers from inception to September 2025. Risk of bias was assessed using the Quality in Prognosis Studies tool. Hazard Ratios were pooled using a random-effects meta-analysis. Subgroup analysis was stratified by variant severity.
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results</jats:title>
<jats:p>
Eight studies (
<jats:italic toggle="yes">N</jats:italic>
= 13,690) were included. The primary meta-analysis (
<jats:italic toggle="yes">n</jats:italic>
= 4947) revealed
<jats:italic toggle="yes">GBA1</jats:italic>
variants were associated with significantly increased all-cause mortality risk versus non-carriers (HR 1.53, 95% CI 1.24–1.87;
<jats:italic toggle="yes">I</jats:italic>
<jats:sup>2</jats:sup>
= 0.7%). 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.
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>
<jats:italic toggle="yes">GBA1</jats:italic>
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.
<jats:italic toggle="yes">GBA1</jats:italic>
status should be considered a significant prognostic factor for stratification in clinical trials and management.
</jats:p>
</jats:sec>
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