A decade after its founding, the International Parkinson Disease Genomics Consortium (IPDGC) is looking back on on its first 10 years of research and outlining its goals for the future.
IPDGC was started in 2009 by a small group of researchers who thought that collaborative efforts were necessary to further understanding of the genetics of Parkinson’s disease (PD).
The group has now published a paper, titled “Ten Years of the International Parkinson Disease Genomics Consortium: Progress and Next Steps,” in the Journal of Parkinson’s Disease, in which they reflect on the progress they’ve made and where they hope to go from here.
It has long been thought that genetics might play a role in Parkinson’s, and this question has been the subject of much research. In the early 2000s, this field was extremely competitive and not very collaborative.
“The stakes were high, there was little reward for second place … and there was little mechanism for shared success,” the researchers wrote.
Beginning around 2005, however, technological advancements and initiatives such as the Human Genome Project started to facilitate genetic research with data on a scope and scale that had not been possible before. Critically, the more data available for these analyses, the more powerful they are — and as such, there was a strong need for data-sharing and collaboration.
“The IPDGC was born out of a realization that no single investigator could deliver on the promise of modern human genetics in isolation,” co-author Andrew Singleton, PhD, of the National Institutes of Health, said in a press release. “We realized that to truly leverage the incredible gains in genetic technologies in the PD space, at scale, would require a highly collaborative approach.”
IPDGC was the result of a 2009 meeting that included about 10 researchers in Paris. Since then, the group has grown to more than 100 researchers around the world. They hold annual meetings, and recently started new research initiatives in Africa and the Middle East — most of their research to date has focused on populations in Europe and the U.S.
“The coordinated analysis of genome-wide association (GWA) data was perhaps the first success for IPDGC and has continued to be a mainstay of our work,” Singleton said.
GWA involves looking for genetic variations that tend to be associated with a particular condition — in this case, Parkinson’s. The IPDGC has performed GWA studies using data its researchers have collected as well as data from industry collaborators such as 23andMe.
While the first of these efforts only included about 3,000 people, the most recent study had data for more than 50,000 people with Parkinson’s, as well as roughly 1.4 million people used as controls.
“As in other disorders, as sample size has grown, so has power and the number of loci detected,” the researchers wrote. “Currently, there are more than 90 known risk loci for [Parkinson’s].” (Loci are positions on a chromosome where a particular gene or genetic marker is located.)
Beyond the identification of risk loci, collaborations fostered by the IPDGC have also helped in understanding the biological processes underlying Parkinson’s disease. For example, such research revealed that Parkinson’s is associated with changes in the tissue of the brain itself, particularly in the cells of a region called the substantia nigra. This contrasts with Alzheimer’s disease, where similar dysregulation is typically seen in immune cells, not the brain cells themselves.
IPDGC’s research has also led to the discovery and validation of previously unknown pathways associated with the disease, and how mutations in these pathways can affect disease risk, such as how mutations in the VPS13C gene can be a cause of early-onset Parkinson’s disease.
This research has also contributed to the estimation that 16–36% of Parkinson’s risk has some kind of genetic basis.
Future work anticipated by the IPDGC includes more research to better understand the genomic architecture of Parkinson’s, particularly in groups of non-European descent, which have historically been understudied. This also involves more detailed studies looking for links between genetic variations and particular aspects of how Parkinson’s manifests from person to person.
The group also hopes to continue to facilitate efforts to build larger research cohorts and to share data and resources among researchers. For instance, one tool in development is the IPDGC sequencing browser, which allows users to look at sequence information for IPDGC data. Another, the IPDGC GWAS browser, is a community-driven site aimed at identifying previously unknown Parkinson’s genes.
“While we believe the work of the IPDGC has had a significant and lasting impact on our field over the last ten years, we are even more excited by the course we have charted for the next decade,” Singleton said.