A little more than 20 years ago, we thought Parkinson’s had no genetic connection. Today scientists have a growing list of genetic variants and mutations linked to the disease. While we’ve learned a lot in two decades, we know there is more to discover. How do we do it?
Research volunteers give DNA samples; scientists compare and contrast the DNA of people with Parkinson’s and people without the disease — what is different, what is the same? These large analyses are called genome-wide association studies or GWAS.
Previous studies using this strategy, in part supported by The Michael J. Fox Foundation (MJFF), have identified a number of potential genetic risk factors. A new study, the largest of its kind yet performed for Parkinson’s disease (PD), confirmed some previously reported risk factors and identified 17 new genetic variants associated with PD. These findings published this week in the journal Nature Genetics.
Researchers from genetic testing company 23andMe, biotechnology company Genentech and the National Institute on Aging (part of the National Institutes of Health) looked at data from 425,000 people. Most of those people came from the 23andMe database — including the 10,000-strong 23andMe Parkinson’s Research community — and PDGene, an online library of published Parkinson’s research genetic data funded by MJFF.
“We know there is much to learn about Parkinson’s genetics and how these factors lead to disease,” says Brian Fiske, PhD, MJFF senior vice president of research programs. “The large-scale needed to make these discoveries can only succeed with the partnership of hundreds of thousands volunteering their DNA for analysis.”
MJFF is working with 23andMe, Genentech and the National Institute on Aging on a number of initiatives to learn more about Parkinson’s and advance treatments to stop progression.
Tracking Genes to Dysfunction and Disease
What happens after a discovery like this? Scientists will look at the role those genes play in the body and if people with Parkinson’s have dysfunction in those places. That abnormality may be involved in the disease, and researchers may be able to make drugs that correct the dysfunction and stop disease.
An example: Some people with Parkinson’s have a mutation in the LRRK2 gene. Those mutations cause heightened activity of the LRRK2 protein. Drug developers are making LRRK2 inhibitor drugs to lower that activity and hopefully stop Parkinson’s progression.
The genes linked to Parkinson’s from this latest GWAS play a role in lysosomal and autophagy systems, sometimes referred to as the cell’s trash collection and recycling systems. We’re already doing a lot of work in this area. Read more on what we know about autophagy in Parkinson’s disease.
“Genetic research is a bit like a treasure hunt, where each clue unlocks the next,” says Dr. Fiske. “These genetic findings show us where to look for what else goes wrong in Parkinson’s and what we may fix to stop the disease.”