Robert Loughnan
Research Associate, Laureate Institute for Brain Research
1 active project
Parkinson's Disease, Pesticides and Iron Dysregulation
Scientific Questions Being Studied
Parkinson’s disease (PD) is the fastest growing neurodegenerative disorder, with rates of affected individuals expected to double in the next two decades. Paraquat is a pesticide that has been associated with increased risk for PD and is thought to be a driver behind higher rates of PD in rural vs urban areas, although banned in China and the EU this pesticide is still legal in USA. Additionally, iron levels have been shown to be disrupted in key brain regions in PD patients. Recent work in animal model work suggests that the chemical reaction underlying the damaging effect of paraquat may be catalyzed by iron. Here we aim to test if genetic variants known to increase iron levels in specific brain regions (e.g. C282Y) exacerbate the damaging effect paraquat imparts increasing PD risk. We expect that individuals with genotypes for excessive brain iron accumulation (C282Y +/+) and who live in rural areas will have higher PD burden than those that do not harbor this mutation.
Project Purpose(s)
- Disease Focused Research (Parkinson's disease)
- Population Health
- Ancestry
Scientific Approaches
For this research we will use logistic regression models to investigate variables associated with PD risk. Firstly, we will attempt to verify the recent finding made by our lab that C282Y homozygosity in males imparts a nearly 2 fold risk for PD. Next, we will attempt to validate previous research establishing an increased PD burden for individuals living in rural areas. Finally, we will see if C282Y homozygosity interacts with rural status to impart a greater PD disease burden. We will make sure include age, sex and top 10 principal components of genetic ancestry as covariates to try to control for population stratification effects that could confound our analysis.
Anticipated Findings
We expect that individuals with genotypes for excessive brain iron accumulation (C282Y +/+) and who live in rural areas will have higher PD burden than those that do not harbor this mutation. If this proves true, it will provide a link in our understanding of how two known risk factors, one environmental and one genetic, interact to increase PD risk. In addition, it may provide further evidence for policy makers to guide decisions in the use and regulation of paraquat.
Demographic Categories of Interest
- Geography
Data Set Used
Controlled Tier
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