A group of Nigerian, British, and U.S. doctors have discovered a genetic variant that increases the risk of Parkinson’s disease in people of African and mixed-African descent and is not seen in those with European ancestry, a finding that could improve treatment of the movement disorder in a vastly underserved population.
“It could be a major mechanistic basis of Parkinson’s disease in African populations,” the researchers said in their paper, published this week in Lancet Neurology, noting that understanding ancestry-specific risk for the disease was “a particularly crucial point as the Parkinson’s disease field moves towards targeted treatments in clinical trials.”
Studies show Black patients are far less likely to be diagnosed with the disease than others, and, when they are, they’re diagnosed an average of four years later than white patients. Parkinson’s disease affects an estimated 1 million older Americans and 8.5 million people globally; it is unclear how many Black Americans are affected, or if they are at higher risk, because they have rarely been included in genetic and other research.
“Our current understanding of Parkinson’s disease is disproportionately based on studies of populations of European ancestry, leading to a substantial gap in our knowledge about the genetics, clinical characteristics, and pathophysiology in under-represented populations,” the authors wrote, stating that their work is the first genome-wide assessment of Parkinson’s disease genetics in a population of African descent.
The study’s co-lead author Mie Rizig, a senior research clinical fellow at University College London of Sudanese descent, said she had come to see in her postdoctoral research that “despite substantial advances in the genetics of movement disorders — almost no research had been done in patients from African descent.” The new study, she hopes, could shed light on whether therapies now under development based on genetics of people with European descent will also work in Black populations or “would illuminate novel targets for a next generation of strategies.”
Rizig and the research team found the new variant in the GBA1 gene, which is known to carry other mutations that increase the risk for Parkinson’s. People with one copy of the gene were 1.5 times more likely to have Parkinson’s, and people with two copies were 3.5 times more likely to have the disease, which causes tremor, as well as other problems with movement and balance and can lead to issues with walking, sleeping, and remembering. Other GBA1 variants have been linked to increased risk for Parkinson’s in people of Ashkenazi Jewish descent.
The findings startled researchers. They had launched the project simply as a training exercise to teach scientists in Nigeria and elsewhere how to conduct genome-wide studies. “We were completely surprised,” said Sara Bandrés-Ciga, a study co-author and National Institutes of Health staff scientist.
The variant was found in 39% of cases assessed in the study. The exact mechanism of the new variant is not yet known, but initial studies suggest that, like other mutations in the gene, it leads to lower activity of the glucocerebrosidase (GCase) enzyme, which also plays a role in Gaucher disease, a rare genetic disorder caused by problems with lysosomes, tiny sacs in cells that recycle proteins.
Therapies for Parkinson’s that work to increase GCase enzyme activity based on previous genetic studies are currently in clinical trials; the researchers said the new research opened avenues into finding novel mRNA-based and other strategies that could reduce lifetime risk of the disease.
In the study, researchers conducted a genome-wide association study that included nearly 1,500 people of African and mixed-African ancestry with Parkinson’s disease with nearly 200,000 control subjects of African and mixed-African ancestry. The participants came from Nigeria and four U.S. sites.
The search for genetic risk factors in non-white populations has been difficult because most genetic databases are overwhelmingly white. In this study, the researchers sought participants from two studies with large numbers of Black participants: the Nigerian Parkinson Disease Research Network, which is part of a multinational consortium seeking to understand the disease in Africans, and the U.S.-based Black and African American Connections to Parkinson’s Disease study, which has been collecting blood and saliva samples. The researchers also included participants who had consented to having their DNA used for research by the genetic testing company 23andMe.
While any new treatments based on the findings are likely decades away, the research shows the feasibility and importance of studying racially diverse populations. Njideka Ulunma Okubadejo, a co-author and neurology professor at the University of Lagos College of Medicine, said in a statement that the new work is a step toward a future “where the research field is prioritizing, learning from, and treating all people with Parkinson’s disease.”
The work was conducted by the Global Parkinson’s Genetic Program, which seeks to understand the genetic architecture of the disease and is part of a larger initiative funded by the Sergey Brin Family Foundation and implemented by the Michael J. Fox Foundation for Parkinson’s Research.