Integrating Environmental, Genomic, and Functional Data to Characterize Individual Risk for Parkinson's Disease
Abstract
The overall purpose of this work is to characterize which individuals may be susceptible to specific toxic insults, and the underlying mechanisms. We have three Aims: 1) use iPSC-derived neuronal cell lines to validate and extend our prior work that found an 11-fold increased risk of Parkinson's disease (PD) in persons exposed to the herbicide paraquat who lacked functional glutathione-S-transferase T1 (GSTT1), a key metabolic enzyme with anti-oxidant function; 2) perform whole genome sequencing of existing DNA specimens from a PD study with highly characterized pesticide exposures, using bioinformatic tools to identify likely functional gene-environment interactions; and 3) test our predictions using iPSC-derived neuronal cell lines that model these genetic variations, and exposing cellular lines to these same environmental agents. This is a partnering PI project with W81XWH-20-1-0710. The scope of the -0709 project is to accomplish Aim 2. To date we have completed sequencing of genomic DNA of 270 individuals, 5 more than specified in the SOW. In combination with existing sequencing data for this population we now have sequencing data for 340 study participants. Using a range of curation approaches and imputation of GWAS data we have and continue to identify compelling gene-pesticide interactions. In the next year of the project we will incorporate sequencing data to identify likely causal variants which will be validated as Aim 3 by the partnering PI.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2021
- Accession Number
- AD1149992
Entities
People
- Samuel M. Goldman