Multi-Ancestry Genetic Study of Parkinson’s Disease Identifies New Risk Genes in Pursuit of Novel Treatment Targets

Sixteen research centers from across the globe have published results from largest, most genetically diverse study on the genetic causes of Parkinson’s disease (PD) to date. Collaborators working under the Aligning Science Across Parkinson’s Global Parkinson’s Genetics Program (ASAP-GP2) published a study in Nature Genetics that used data from almost 50,000 PD patients of European, East Asian, Latin American and African ancestry.

The study identified 78 risk loci, including 12 novel loci that contain about 25 genes potentially associated with the disease. The findings also improved understanding of 23 already known loci by narrowing down specific variants in these regions.

The case for inclusive research

The results demonstrate how collaborating on inclusive, global research advances inclusivity in healthcare. Although some progress has been made in identifying genetic variants that contribute to PD, most of the research has been performed in western European populations.

“Studying diverse populations improves healthcare research for everyone,”explains the study’s co-corresponding author, Ignacio Mata, PhD, a researcher with the Genomic Medicine Institute in Cleveland Clinic’s Lerner Research Institute, one of the 16 participating research centers. “If the same variant is associated with Parkinson’s disease across people of diverse ancestry living in different environments, we can imagine that the association is less likely to be random.”

The genetic basis of PD is highly complex; variation in many genes can cause the neural degradation associated with the disease, and only some of these genes are related. Lack of genetic diversity in research data makes it more difficult to understand the role of these genes in underrepresented populations, increasing health disparities and limiting potential treatment options.

This collaboration formed out of the Global Parkinson’s Genetics Program (GP2), an international research program managed by the Michael J. Fox Foundation and funded by Aligning Science Across Parkinson’s. GP2 connects PD research efforts around the globe and supports recruitment of and collection from diverse research participants, along with providing genetic studies for free and sharing all the data with the scientific community. Dr. Mata serves on the steering committee for the group, which spans over 100 research sites across all six populated continents of the globe, and co-leads its working group on underrepresented populations.

“Due to the limitations of these types of genetic studies, when people work on their own cohorts, they tend to move the field forward slowly, through small discoveries,” notes Dr. Mata. “When we bring people together and share our resources, skills and training as a team, we move discovery forward at a much faster rate. This is particularly important for those working with populations who historically have been underrepresented and in many cases are underserved.”

Over the years, GP2 also teamed up with 23andMe, a company that provides genetic testing at home. 23andMe has offered its customers the option to contribute their genetic data to PD research since 2009. The company has large cohorts of individuals with African, East Asian and Latin American ancestry.

Uncovering genetic variants to find druggable targets

In total, the study analyzed data from 49,049 individuals with PD, 18,618 individuals whose immediate relatives had the disease and 2,458,063 neurologically healthy controls. What they found was staggering.

“When we saw the combined results of our studies, we were blown away,” says Dr. Mata. “We found 12 new loci to study and were able to narrow down to one to five specific variants in 23 loci that we already knew about. Identifying specific variants is crucial in providing the right targets for functional studies and ultimately proving whether a gene has a role in neurodegeneration.”

Identifying variants is also crucial in developing medications to block the neurodegenerative process, he adds. GP2 and its collaborators will investigate the genetic variants uncovered in their study, with the goal of finding druggable targets. They also are working to add more data from other populations to the study.

Accelerating progress through genetically diverse studies

“This project is proof that collaborating on large-scale genetically diverse studies advances the field at a much faster rate.,” Dr. Mata says. “We are committing to recruiting even more individuals of non-European ancestry to increase the genetic diversity of future studies. This is the future of genetic research.”

The study was funded by Aligning Science Across Parkinson’s and managed by the Michael J Fox Foundation. It is the result of a close collaboration between research centers in the United States, United Kingdom, Singapore and Peru.