LARGE-PD: Linking Genes in Large Way in Latin America
“I realized the huge impact that studying new communities could have on our research ... PDF also saw that potential and has helped us make it happen. The implications for PD research are exciting.”
Ignacio Mata, Ph.D.
(Pictured above: the LARGE-PD team and PDF Research Advocates-Photo Credit: Ignacio Fernandez Mata, Ph.D.)
Who among us is likely to have a genetic mutation that may increase the risk of Parkinson’s disease (PD)? While genetic mutations in PD are rare, studying them helps scientists learn about the disease — how it develops, how it progresses and how it may be treated — not just in the individuals who have the genes, but in anyone who has Parkinson’s disease.
We have some understanding of the genetic factors that increase a person’s risk of developing PD, but according to Ignacio Fernandez Mata, Ph.D., and Cyrus Zabetian, M.D., our knowledge is limited because the majority of genetic studies for PD are carried out in populations of European and Asian ancestry, leaving out individuals in other areas of the world. With the help of Drs. Mata and Zabetian, who are affiliated with the VA Puget Sound Health Care System and the Department of Neurology at the University of Washington, this is changing.
Six years ago, aided by a grant from the Parkinson’s Disease Foundation (PDF), they created the first large-scale survey of PD genetics in Latin America: the Latin American Research Consortium on the Genetics of PD (LARGE-PD).
In just a few years, LARGE-PD has become an essential resource — a repository of DNA samples that are linked with demographic, clinical and environmental exposure data that provides opportunities to study PD-related genes, and perhaps discover new ones.
Drs. Mata and Zabetian knew that for LARGE-PD to be successful, they would need to collaborate with peer scientists in the region. They used two years of funding from PDF’s International Research Grants program to set up partnerships with six scientific institutions in five countries: Argentina, Brazil, Colombia, Peru and Uruguay.
Working with their colleagues, Drs. Mata and Zabetian were able to collect blood samples and data from more than 3,500 people — both those with Parkinson’s disease and healthy controls. With this wealth of information at their fingertips, they and their colleagues began uncovering new information about PD and genetics.
For example, they found that mutations in LRRK2 and GBA, two of the most important genes linked to PD, are common in Latin America but vary in prevalence and distribution by country. This variation is in part determined by how much European DNA is present in the population. In particular, the frequency of GBA mutations was twice as high in Colombia as in the US or elsewhere in Latin America, because of a mutation only seen in Colombia.These findings suggest that the genetic factors that influence the risk for PD in Hispanic populations are somewhat different than in people of European descent. Even among Hispanics, genetic risk for PD might vary depending on the origin of a person’s ancestors.
Drs. Mata and Zabetian say that the key to the project’s success has been their collaborators. Rather than having one or two people conducting studies over time, they have a large group of scientists in five countries studying different pieces of the data at the same time, which speeds the work. In the near future, they hope to add partners in Ecuador and Venezuela. And to their delight, the collaboration has spread into other areas of PD research. For example, as the group worked together, they realized that in order to study cognition and PD in their communities, the standard cognitive tools must be adapted to Spanish and Portuguese languages. PDF provided support to generate a protocol for this project.
Six years ago, LARGE-PD was chosen for PDF funding because it was innovative and had potential to fill a gap in our understanding of PD. The investment has clearly been worthwhile — improving our understanding of the genetic susceptibility for PD in Hispanic populations.
“I realized the huge impact that studying new communities could have on our research,” said Dr. Mata. “When I saw the excitement and tremendous effort from other scientists, I realized that this could develop into something much bigger. PDF also saw that potential and has helped us make it happen. The implications for PD research are exciting.”
LARGE-PD was funded through PDF’s International Research and Advancing Parkinson’s Treatments Programs. In 2014, PDF is supporting these multi-grant programs respectively with $742,500 and $499,500 and is supporting student fellow Andres Lescano to assist the LARGE-PD project in Uruguay with a grant of $5,000.