Genetic variations along with exposure to environmental factors, such as pesticides, may increase Parkinsons disease in a sex-dependent manner, a study of French farmworkers suggests.

Most cases of Parkinsons disease dont arise from a single factor, but rather a combination of a persons genes, lifestyle, and what theyre exposed to in the environment, Michael Kobor, PhD, who co-led the study from the University of British Columbia (UBC) in Canada, said in a university press release.

Studies like ours provide building blocks for investigation of personalized risk profiles for Parkinsons disease and biomarkers for earlier diagnosis, said Samantha Schaffner, PhD, a postdoctoral fellow at UBCs Edwin S.H. Leong Centre for Healthy Aging, who noted that, while its too early to know if the findings will hold true when looking at larger pools of data, in the future, [scientists] may be able to estimate someones risk level based on their sex, genetics and lifestyle, and provide tailored guidance on prevention.

The study, Genetic variation and pesticide exposure influence blood DNA methylation signatures in females with early-stage Parkinsons disease, was published in npj Parkinsons disease by Kobors team in collaboration with researchers in France.

How Parkinsons starts is unclear, but growing evidence points to how genetics and a number of environmental factors, such as breathing in or having contact with pesticides, may come together to cause the disease.

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, said Kobor, a Canada research chair in social epigenetics, who is leading efforts to establish a link between genetics and pesticide exposure. Were working to bring these pieces of the puzzle together to gain a better understanding of how Parkinsons develops, whos most at risk, and how we can prevent it.

The study included 71 people with early-stage Parkinsons and 147 people without it who were enrolled with TERRE, a health database of French agricultural workers that contains a detailed history of pesticide exposure.

People exposed to pesticides used in farming are at a higher risk for developing Parkinsons and those who live or work near areas with higher levels of certain pesticides are more likely to see their symptoms get worse faster.

Here, the researchers focused on DNA methylation and how its patterns change in women versus men with Parkinsons. In DNA methylation, chemical marks on DNA can indicate whether genes are turned on or off, that is, how the information in genes is used by cells without changing the genetic code itself.

After scanning more than 42,000 regions of DNA from blood samples, the researchers found that DNA methylation linked to early-stage Parkinsons was spread across 69 regions in women and only two in men.

In women, DNA methylation mapped to genes related to cell signaling, protein production, and ion transport. In men, those epigenetic changes mapped to genes related to protein breakdown or recycling and the transport of ions within cells.

To validate their findings in women, the researchers downloaded the PEG1 (GSE111629) and SGPD (GSE145361) datasets from a public database. They found a significant match in DNA methylation between TERRE and PEG1 along with a French database called DIGPD, but not between TERRE and SGPD.

For 48 of the 69 regions targeted by DNA methylation in women, genetics alone provided the best explanation for the epigenetic changes previously attributed to Parkinsons, but pesticide exposure also contributed, especially when it interacted with genetic factors.

These findings highlight the complex interactions between genetic and environmental factors, Schaffner said. Having certain genetic variations may only increase Parkinsons disease risk in the context of an environmental exposure like pesticides, and they might have a sex-dependent effect on risk.

While this study may help lead to a more personalized approach to Parkinsons based on a persons genetic makeup, the findings should be further explored in larger study populations and in experimental systems, preferably with precise measures of exposure, the researchers said.

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