, attendees at the International Congress of Parkinson’s Disease and Movement Disorders were told.
Dr. Ignacio F. Mata
“Through the years, as we’ve increased the number of individuals that we’ve included in our genetic studies, the number of risk factors that we’ve been able to identify has increased exponentially,” said Ignacio F. Mata, PhD, a neurogeneticist and principal investigator with the Genomic Medicine Institute of the Cleveland Clinic Lerner Research Institute. “This is all due to collaborations.”
Dr. Mata reviewed no fewer than seven initiatives that are gathering genetic data from people with Parkinson’s disease in Central and South America, India, China, Africa, Oceania, the Middle East, and Central Asia, along with efforts to target diverse populations in London and African Americans in the United States.
“One of the problems that we’ve had in the past is that most of the studies have been done just with individuals that are of European ancestry, so there’s a big gap of other populations that we haven’t been able to study,” Dr. Mata said. “And this is true for all of the current studies that are ongoing here in the United States.” That includes the Parkinson’s Progression Markers Initiative, he said, in which fewer than 6% of participants are non-European. Dr. Mata is also the lead in the Global Parkinson’s Genetics Program (GP2) for underrepresented populations.
Lack of diversity in genetic studies isn’t an issue in Parkinson’s studies alone, Dr. Mata said. “This is a generalized problem across all genetic studies,” he said, citing a 2016 analysis that found the proportion of participants in genome-wide studies was 96% European descent in 2009, shifting to 80% by 2016. “There’s still a big gap because most of the non-European populations came mostly from Asia,” Dr. Mata said, with Latinos and people of African descent representing less than 1% of the study populations.
In an interview, Dr. Mata noted there are a multitude of reasons for enrolling more diverse populations. “We’re going to be able to use genetics to create new treatments and do risk prediction – the so-called precision or personalized medicine,” he said. “We’re leaving a big chunk of the population behind if we don’t include those individuals.”
Scientific basis for diversity
There are a multitude of scientific reasons for doing so, too, said Dr. Mata. “In the whole genome we try to find gene variants that modify the risk for certain disease,” he said. “These regions can be quite large, so increasing the number of individuals that come from different genetic backgrounds can actually help us reduce the number of regions that need to be studied to find the causal variants.”
Andrew Singleton, PhD, director of the Center for Alzheimer’s and Related Dementias at the National Institute of Aging in Bethesda, Md., concurred that enrolling more diverse populations can speed up research for targeting genetic variants.
Dr. Andrew Singleton
“We can use the differences in genetics to narrow down our search for variants, reduce the places where we’re looking for risk variants, and reduce the number of genes we’re looking at,” he said in an interview.
Roy Alcalay, MD, professor of neurology at Columbia University Irving Medical Center in New York, offered two more scientific reasons for more diverse study populations “in addition to being more ethically appropriate,” he said. “One is, you may identify new genes that you wouldn’t have identified otherwise; and also in the genes that already exist, you may recognize that some of the pathogenic variants may be more prevalent in populations that were unknown.”
One of the challenges in casting a wider net is that much of the research funding has been concentrated in the United States and Europe, Dr. Mata said. And even in the United States, with large, diverse populations, minority groups are underrepresented in these studies, he said, but a potential solution is emerging. “This is something that we’re learning now with COVID,” he said. “We can do a lot remotely. This should help bring some of those barriers down.”
Cultural barriers are also foreboding. “Individuals may not feel comfortable participating in research,” he said in the interview. “I see this especially in the Hispanic community; many don’t understand what they can do with genetic material, or they’re afraid it will be shared with police, and if they’re here in nonofficial immigration status, they’re afraid they could be deported. There are a lot of misconceptions about genetic research.”
An initiative of the Parkinson’s Foundation PD GENEration Study is to provide free genetic tests and give the patient a report on genetic counseling “to empower patients,” Dr. Mata said.
Solutions for targeting underrepresented groups are emerging, Dr. Singleton said. “Actually there’s a really elegant solution, which is that in the populations that we go into and work with, we make sure the ownership of those cohorts, the ownership of the science and the analysis belongs to those populations,” he said.
“Part of that is creating infrastructure on site,” Dr. Singleton added. “Another part is providing training and outreach so we can help to train a whole new generation of scientists and researchers who can work in those populations embedded within those populations. They’re really the champion of moving that research forward.”
Dr. Alcalay credited Dr. Mata for his work with cohorts in Central and South America and in reaching out to other countries to recruit more diverse populations for genetic Parkinson’s studies. “And it’s not just because it’s the politically correct thing to do, about inclusivity and diversity,” Dr. Alcalay said. “It’s because it’s really meaningful. In addition to being ethically more appropriate, it will advance the entire field.
“I also really think it’s a no-brainer,” Dr. Alcalay said. “It’s something that needs to happen.”
Dr. Mata receives grant funding from the National Institutes of Health. Dr. Singleton and Dr. Alcalay have no relevant disclosures.