Parkinson’s disease affects nearly 10 million people globally. Yet, much remains unknown about the triggers behind the disease.
Now, an international collaboration between UBC’s Edwin S.H. Leong Centre for Healthy Aging and researchers in France is shedding light on how genetics and environmental exposures come together to shape a person’s risk of developing the condition — potentially laying the groundwork for earlier detection and tailored prevention strategies.
The study, published in npj Parkinson’s Disease, looked specifically at pesticide exposure — one of the most well studied environmental risk factors for Parkinson’s disease. Previous research has shown that people regularly exposed to pesticides, particularly agricultural workers and farmers, have a substantially higher risk of developing the neurodegenerative disorder.
However, not everyone who sustains long-term exposure to pesticides develops Parkinson’s disease. This led the researchers to explore what other factors might be at play.
“Most cases of Parkinson’s disease don’t arise from a single factor, but rather, it’s a combination of a person’s genes, lifestyle and what they’re exposed to in the environment,” says senior author Dr. Michael Kobor, a professor of medical genetics and the Edwin S.H. Leong UBC Chair in Healthy Aging – a UBC President’s Excellence Chair.
“We’re working to bring these pieces of the puzzle together to gain a better understanding of how Parkinson’s develops, who’s most at risk, and how we can prevent it.”
Dr. Michael Kobor
“While there has been a great deal of research into each of these factors on their own, we have a limited understanding of how they interact with each other. We’re working to bring these pieces of the puzzle together to gain a better understanding of how Parkinson’s develops, who’s most at risk, and how we can prevent it,” adds Dr. Kobor, also a Tier 1 Canada Research Chair in Social Epigenetics.
Examining epigenetic changes
For the study, Dr. Kobor and his team collaborated with researchers in France to analyze blood samples from unique cohort of French farm workers with early-stage Parkinson’s disease, known as TERRE, which includes a detailed history of pesticide exposure. They looked at changes in the epigenome — tiny molecules that attach to DNA and have the ability to turn genes on or off, like a light switch, known as DNA methylation.
DNA methylation changes have previously been detected in people within a year of a Parkinson’s disease diagnosis, suggesting that this may serve as a part of a molecular blueprint for the causes of the disease.
The researchers looked for patterns between these epigenetic changes and an individual’s history of pesticide exposure, biological sex and genetic profile. They found that there were more epigenetic changes in women with early-stage Parkinson’s disease compared to men, and that most of the changes were associated with a person’s genes rather than pesticide exposure.
The findings suggest that person’s genetic makeup, and to a lesser degree how genetics and pesticide exposure interact, contribute to variability in Parkinson’s disease risk.
“These findings highlight the complex interactions between genetic and environmental factors,” says lead author Dr. Samantha Schaffner, a postdoctoral fellow at the Edwin S.H. Leong Centre for Healthy Aging. “Having certain genetic variations may only increase Parkinson’s disease risk in the context of an environmental exposure like pesticides, and they might have a sex-dependent effect on risk.”
Shaping precision medicine
The researchers hope the findings will help pave the way toward a more personalized approach to Parkinson’s disease.
A deeper understanding of the interplay between genetics, the environment and biological sex could lead to development of more precise and individualized risk profiles. This could be used to identify people who are at a high risk of Parkinson’s disease earlier and open the door for targeted interventions that would help people reduce their risk.
“In the future, we may be able to estimate someone’s risk level based on their sex, genetics and lifestyle, and provide tailored guidance on prevention.”
Dr. Samantha Schaffner
“Studies like ours provide building blocks for investigation of personalized risk profiles for Parkinson’s disease and biomarkers for earlier diagnosis,” says Dr. Schaffner. “In the future, we may be able to estimate someone’s risk level based on their sex, genetics and lifestyle, and provide tailored guidance on prevention.”
While the research team notes that further studies are need in larger population samples, the findings offer valuable new insights in understanding Parkinson’s disease. It reinforces the need to consider a variety of lifestyle and genetic factors to uncover the root causes of this challenging condition.
This study was supported by the Canadian Institutes of Health Research, the French National Research Agency, and the Federal Ministry of Education and Research of Germany.