Study Rationale:
Pesticide exposure is among the most consistently and widely reported environmental risk factors for Parkinson’s disease (PD). However, research on specific pesticides in population-based studies of people with PD have been limited. Furthermore, little data exists to help identify biological pathways and physiologic responses to common and widely used pesticides that may contribute to PD in humans.
Hypothesis:
We hypothesize that chronic, low-level pesticide exposure from living or working near agricultural farms may be related to biological changes leading to PD onset and development of symptoms. We aim to use large biological data sets to identify novel targets inside cells that interact with pesticides associated with PD. In addition, we will describe cellular pathways that are impacted by pesticide exposure in patients.
Study Design:
We will investigate the role of pesticides in PD susceptibility and progression, analyzing records of agricultural-pesticide application. The CA-PUR database has information from 1974 to 2018 on 200+ pesticides. We will apply a systems biology approach with high-throughput data (methylome and metabolome) to a large, population-based study of PD from the California Central Valley (n=1,870), with periodic follow-up to monitor symptom development (n=550, 5 to 7 years). We propose an agnostic “pesticide-wide association study” in PD followed by systems biology analysis of PD-related pesticides.
Impact on Diagnosis/Treatment of Parkinson’s disease:
This study will shed light on how biological systems operate and interact in response to pesticide exposure and early PD pathology. This research aims to improve our understanding of how environmental toxicants interact with cellular pathways inside cells. Furthermore, a primary goal of this research is to provide epidemiological evidence related to specific pesticides and pesticide co-exposure profiles to drive preventative policy around these agents. We ultimately aim to improve prevention efforts, advance therapeutic development, and inform public policy on pesticide regulation.
Next Steps for Development:
Follow up studies will investigate the impact of the identified pesticides/clusters on biological networks.