Parkinson’s mutations seen in nearly 13% of PD GENEration patients
Genetic testing suggests disease-related variants more common than thought
Nearly 13% of people with Parkinson’s disease in North America carry a Parkinson’s-associated genetic mutation, according to new data from the PD GENEration study.
This suggests that genetic variants with a link to Parkinson’s are more common than previously thought.
“The positivity rate and the high interest in getting [genetic testing] will hopefully translate to increased participation in observational studies and clinical trials toward therapies targeting these genes, simplifying precision medicine clinical trials in [Parkinson’s],” Roy Alcalay, MD, lead principal investigator for PD GENEration at Columbia University in New York, said in a Parkinson’s Foundation press release.
Findings were detailed in the study, “Parkinson’s disease variant detection and disclosure: PD GENEration, a North American study,” published in Brain. The work was funded by the Parkinson’s Foundation.
Lacking of genetic testing for Parkinson’s thought to hinder therapy advances
While the causes of Parkinson’s aren’t fully understood, it’s well established that genetic mutations, in some cases, underlie the disease. Yet, because of barriers like cost and lack of awareness, most people with Parkinson’s never undergo genetic testing to know if they carry a disease-linked mutation. This has been a major obstacle for clinical trials of experimental disease treatments aiming to target specific mutations.
The Parkinson’s Foundation launched the PD GENEration study (NCT04057794, NCT04994015) five years ago aiming to fill this gap. The observational study offers free genetic testing and counseling to Parkinson’s patients, including options for at-home testing and counseling in multiple languages, with the goal of testing tens of thousands of adults for Parkinson’s-related mutations.
Researchers reported on study findings as of mid-2023. More than 10,000 people had undergone genetic testing for Parkinson’s, with results available for 8,301 of these patients.
“PD GENEration stands at the forefront of precision medicine and the potential for tailored treatments,” said Lola Cook, a genetic counselor at Indiana University and the study’s first author.
Results showed that 12.9% of these patients carried a known Parkinson’s-related mutation. The most commonly affected gene was GBA1, with mutations found in 7.7% of the adults. Mutations in the genes LRRK2 and PRKN were also fairly common, each found in more than 2% of participants. Mutations in other Parkinson’s-related genes collectively affected less than 1% of the patients.
Mutations found 9% of patients without known Parkinson’s risk factors
Certain factors previously have been associated with higher rates of Parkinson’s mutations; these include an age at onset earlier than 50, having a close biological relative with Parkinson’s, and having ancestry from certain groups, including Ashkenazi Jewish, Basque, and North African Berber. Among individuals with these risk factors, nearly 1 in 5 (18%) were found to carry a Parkinson’s-related mutation.
But notably, mutations still were quite common among patients without any of these risk factors, with nearly 1 in 10 (9.1%) found to carry a disease-related mutation.
“We did not anticipate the high positivity rate for genetic mutations, specifically the nearly 10% having a positive result even without any known genetic risk factors,” Alcalay said.
Researchers said this finding emphasizes the importance of genetic testing for everyone with Parkinson’s, not just those with known risk factors.
“As trials of gene-specific potentially disease-modifying treatments have begun, and genetic results may impact disease prognosis, possibly for management, and with certainty and clarity related to familial risks, we believe that clinical genetic testing should be offered to all people with Parkinson’s disease to empower them to act upon their genetic findings,” the team wrote.
Although this study included thousands of patients, a notable limitation was the lack of a diverse patient group, with more than 85% of participants identified as white. As such, its findings may not be applicable to populations that aren’t of European ancestry, the researchers said. They stressed a need for further studies in more diverse groups, noting that efforts are underway to recruit patients of various racial and ethnic backgrounds into GENEration.
“As we’ve seen from the study’s enrollment numbers and survey results, there is a strong interest among people with PD [Parkinson’s disease] to push the research effort forward. This includes understanding the disease’s genetics, generally and individually,” Cook said. “It’s the idea that we are all doing our part to move toward improved treatments and a cure.”
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