Consortium is uncovering risk factors that spur disease development in an understudied group
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Approximately 10 million people around the world have Parkinson’s disease. Yet most of the genetic studies on this progressive disorder have been conducted in populations of European and Asian ancestry. Very little is known about the genes that may influence Parkinson’s disease risk in Latinos.
Ignacio Mata, PhD, assistant staff in the Genomic Medicine Institute within Cleveland Clinic’s Lerner Research Institute, is working to change that as the U.S. coordinator of the Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD).
“It’s a very complex disease, and probably every patient has a different combination of variants in different genes,” says Dr. Mata. “That’s why I think it’s very hard to understand the cause and also to slow or stop it.”
In the latest episode of Cleveland Clinic’s Neuro Pathways podcast, Dr. Mata discusses genetics in Parkinson’s disease and the role of LARGE-PD, a multicenter collaboration. He covers:
Click the podcast player above to listen to the 27-minute episode now, or read on for a short edited excerpt. Check out more Neuro Pathways episodes at clevelandclinic.org/neuropodcast or wherever you get your podcasts.
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Podcast host Glen Stevens, DO, PhD: What I’d like to know now is what have you found? What surprised you?
Dr. Mata: The latest [study] we have done is a genome-wide association study, or GWAS, where you compare a very large number of cases with the disease that you are trying to study and a large number of controls that are matched by age, gender and hopefully where they’re coming from in terms of ancestry. And then you look for variants that occur at a different frequency between the two groups. If a variant is more frequent in cases, then it might be a risk variant. In contrast, if a variant is more common in controls, maybe it’s a protective variant.
This association study has allowed us to really start to understand what the genetic architecture of Parkinson’s disease is in Latinos. And we know that it is about 80% similar to Europeans, but there are new genes we have identified that are mostly associated with indigenous and African ancestries.
Dr. Stevens: And what’s the number of causal genes?
Dr. Mata: In total for Parkinson’s disease, we have about 24 that are familial. If you have a variant in those genes, you are most likely going to develop the disease. We call these causal variants. And then there are probably over 100 we have identified that are risk variants. This means that these variants do not cause Parkinson’s but increase a person’s risk. And most of us carry several of these variants. We then use something called a polygenic risk score in which we calculate how many of each type of variant someone carries and this tells us their total risk by comparing all the variants.
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