Polygenic Parkinson's disease genetic risk score as risk modifier of parkinsonism in Gaucher disease

BackgroundBi-allelic pathogenic variants in GBA1 are the cause of Gaucher disease (GD1), a lysosomal storage disorder resulting from deficient glucocerebrosidase. Heterozygous GBA1 variants are also a common genetic risk factor for Parkinsons disease (PD). GD manifests with considerable clinical heterogeneity and is also associated with an increased risk of PD. ObjectiveTo investigate the contribution of PD risk variants to risk of PD in patients with GD1. MethodsWe studied 225 patients with GD1, including 199 without PD and 26 with PD. All cases were genotyped and the genetic data was imputed using common pipelines. ResultsOn average, patients with GD1 with PD have a significantly higher PD genetic risk score than those without PD (P=0.021). ConclusionsOur results indicate that variants included in the PD genetic risk score were more frequent in patients with GD1 who developed PD, suggesting that common risk variants may affect underlying biological pathways. Supplemental data here