Commentary: Pesticides and GBA1 pathogenic variants in Parkinson's disease: An emerging and potentially dangerous...

We comment here on the recently published paper by Ostentag et al., 2026, which examined self-reported environmental exposures in a group of patients with Parkinson's Disease (PD). Patients with GBA1-associated Parkinson's Disease (PD) were two times more likely to have been exposed to occupational pesticides compared to those with idiopathic PD, while there was no difference for any other exposure between the two groups. Combined with previous work, these findings suggest that GBA1 pathogenic variant status in combination with exposure to pesticides leads to a high risk of developing PD, and have several implications: at the genetic epidemiological level, they provide a partial explanation for the missing penetrance of GBA1 pathogenic variants; at the biological level, they suggest that the biological mechanisms of pathogenicity conferred by the genetic predisposition and the environmental exposure may converge on the same pathways, potentially involving the interplay between lysosomal and mitochondrial function; at the public health level, they suggest that exposure to even low levels of environmental toxins may be especially deleterious for genetically susceptible individuals with GBA1 pathogenic variants. Further studies are needed to verify these results using rigorous methods for exposure ascertainment, to identify the exact class of substances underlying this association and their biological mechanisms in this context, and to determine the exposure levels that could be considered safe in this vulnerable population.