A Griffith University senior researcher has co-led a breakthrough study into the non-inherited changes in genes, which can assist scientists in better understanding the interactions between genes and the environment, and how they influence complex diseases like Parkinson's disease.
It is the first large epigenome-wide study to compare changes between people with Parkinson's and those without the disease.
Epigenetics is the study of changes in organisms caused by modification of gene expression, rather than alteration of the genetic code itself.
The researchers studied the epigenetic changes in blood cells from samples taken from around 2000 people, with the vast majority coming from the Queensland Parkinson's Project based at Griffith University.
Professor George Mellick, a Parkinson's disease specialist and senior research leader within the Griffith Institute for Drug Discovery, worked with scientists from the University of Queensland to produce the latest research, which has been published in Nature Communications.
"This is, by far, the most comprehensive study of epigenetics in Parkinson's disease done anywhere," he said.
"While the DNA sequence of genes (the genetic code) controls the structure and function of each cell, there are chemical modifications to the DNA (known as epigenetic tags) that determine which genes are turned on or off in the cell.
"These epigenetic changes are not 'inherited' in the same way as DNA but can be influenced by things like the environment you live in."
The University of Queensland researchers used cutting-edge technology to investigate around 500,000 regions across the entire human genome that are sites for these epigenetic modifications (known as sites of DNA methylation).
In doing this, the researchers were also able to use complicated statistical methods to compare the differences in these changes between groups of people and to integrate this information with extensive genetic information from all these individuals to produce the following findings:
- The technology enabled the detection the different types of white blood cells that are in an individual blood sample (just by studying the patterns of epigenetic modification on the DNA from the sample);
- The patterns of methylation in blood is related to age of the person and to things like whether a person is a smoker;
- And most significantly, there are specific changes to the pattern of methylation around a particular gene – a solute transporter gene called SLC7A11 – that codes for a protein that transports some known toxins into and out of cells and is involved with some biochemical processes known to be implicated in Parkinson's.
Professor Mellick said the above types of epigenetic changes can occur when people are exposed to some of these of toxins.
"One suggestion is that these epigenetic changes reflect a history of exposure to something in the environment that increases the risk for Parkinson's. This fits with our current understanding that exposure to high levels of herbicides and pesticides is a risk factor for Parkinson's," he said.
"But more significant is the fact that, in this study, we relied only on the epigenetic changes in the blood-derived DNA to potentially tell us about past environmental exposures in these people."
While Professor Mellick said it was an early finding, it suggested that studying epigenetics in detail may be a useful way to understand the interactions between genes and the environment and how this influences complex diseases, which may help in identifying people who have been exposed to environmental factors that impact on their risk and help researchers understand and modify the risks.
"Being able to use surrogates (such as epigenetic changes to DNA) to inform an individual's environmental exposure profile may be very important to advance the understanding of many conditions," he said.
"In general it will help researchers learn more about the causes of complex diseases like Parkinson's that impact on more than 100,000 Australians."
The research 'Analysis of DNA methylation associates the cystine-glutamate antiporter SLC7A11 with risk of Parkinson's disease' has been published in Nature Communications.
Funding / acknowledgments
This research was supported by the National Health and Medical Research Council (NHMRC: 1078037, 1078901, 1103418, 1107258, 1127440, 1113400) and the Australian Research Council (ARC: DP160102400 and FT180100186). Support also came from ForeFront, a large collaborative research group dedicated to the study of neurodegenerative diseases and funded by the NHMRC (Program Grant 1132524, Dementia Research Team Grant 1095127, NeuroSleep Centre of Research Excellence 1060992) and ARC (Centre of Excellence in Cognition and its Disorders Memory Program CE10001021). S.L. was supported by an NHMRC-ARC Dementia Fellowship (1110414) and G.H. was supported by an NHMRC Fellowship (1079679). The Queensland Parkinson's Project (QPP) was supported by a grant from the Australian National Health and Medical Research Council (1084560) to G.M. The New Zealand Brain Research Institute (NZBRI) cohort was funded by a University of Otago Research Grant, together with financial support from the Jim and Mary Carney Charitable Trust (Whangarei, New Zealand). We thank Allison Miller for processing and handling of NZBRI samples.
