A global effort to make genetic studies more diverse has led to a discovery about Parkinson's disease, a common brain disorder that can impair a person's ability to move and speak.
A team that included scientists from Lagos, London and the U.S. found a previously unknown gene variant that can nearly quadruple the risk of Parkinson's for people of African ancestry.
The finding, published in August in The Lancet Neurology, suggests that Parkinson's may work differently in people of African, rather than European, descent. It could eventually help scientists develop a treatment specifically for people with this particular gene variant.
It also shows why including typically underrepresented populations in genetics studies "should really be the rule and not the exception," says Ekemini Riley, managing director of Aligning Science Across Parkinson's, a research initiative that helped coordinate the effort.
The discovery was made possible by a coalition of scientists dissatisfied with the way most genetic studies are conducted.
"Our basis of knowledge for genetics in Parkinson's disease was limited to Northern European populations," says Andy Singleton, who directs the Center for Alzheimer's and Related Dementias at the National Institutes of Health.
Studies of European descendants have revealed several gene variants associated with Parkinson's. But many other variants have probably been missed, Singleton says, because they occur in people with genetic backgrounds that haven't been studied.
"So we decided to diversify that endeavor," he says.
To do that, the NIH joined the Global Parkinson's Genetics Program, which includes researchers from around the world. The goal: collect and analyze genetic samples from a diverse group of more than 150,000 people.
The first step was to make sure that members who were helping to collect DNA samples would benefit from the effort, says Sara Bandrés Ciga, a molecular geneticist at the NIH.
"For a project to succeed we have to always ask: is this something you are interested in? Is this something you want to learn? And then take it from there," she says.
Many participants asked for easy access to the genetic information they were collecting and help learning how to analyze it, says Mary Makarious, a data scientist at the NIH.
So the team created an online database and a training curriculum for scientists on the ground.
"Basically, they will be researchers that will tackle the problems," Bandrés Ciga says.
Ultimately, the team produced online training modules in more than 100 languages, covering subjects ranging from bioinformatics to molecular biology.
A surprising success
Less than five years after its launch, the global effort has produced a notable, and unexpected, finding.
This groundbreaking project has its origins in a set of genetic samples from people in Nigeria, the result of a longtime partnership between NIH scientists and Dr. Njideka Okubadejo, a professor of neurology at the University of Lagos.
The data set was considered too small to detect the sort of gene variants that usually affect the risk for Parkinson's, so it was being used in training exercises to familiarize scientists with techniques used to conduct genome-wide association studies.
But when researchers at the University of Lagos began crunching the data, they saw evidence that something might be going on with one particular gene. It's called GBA1 and it affects a cell's internal recycling system.
"We surprisingly found a hit," says Bandrés Ciga, who was involved in conducting the training exercise.
But she and her colleagues from the NIH, the University of Lagos and University College London thought the finding looked too good to be true.
"When you see a result like this, you instantly think, 'I've done something wrong, It's a mistake,' " Singleton says.
The scientists ran all the analyses again, this time including genetic data from U.S. residents of African descent. In all, they now had data from nearly 200,000 people, including about 1,500 with Parkinson's.
And the result held up.
The gene variant was found almost exclusively in people of African descent. Those who carried a single copy of the gene were about 50% more likely to develop Parkinson's. People with two copies saw their risk increase by nearly 400%.
In people of European descent, another variant of the GBA1 gene also raises the risk for Parkinson's. But the variant found in people of African descent affects a different part of the gene and appears to have a different effect on cells.
"If we can then target that specific protein that's gone wrong, or specific molecule, that's the goal, to get to that level of precision," Riley says.
Riley says the finding is especially meaningful to her because she has family from Nigeria.
And she predicts there will be more discoveries about Parkinson's now that genetic studies are going global.
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