Genetic mutations linked to Parkinson's disease are more common than thought

A new study finds that genetic mutations linked to Parkinson's disease (PD) are more common than researchers previously thought. Researchers from the Parkinson's Disease Foundation-supported PD GENEration study (which reached its goal of 15,000 participants ahead of schedule this spring) found that 13% of participants had the genotype of PD, a large observation compared with long-held estimates. Results from the first three and a half years of the study, which looked at a broad cohort across North America, have been published in a peer-reviewed scientific journal. brain.

PD GENEration, which tests for clinically significant Parkinson's-related genes, has been offered by the Parkinson's Foundation to all people diagnosed with Parkinson's since 2019. The study is the first to return results at scale through live genetic counseling in English or Spanish, allowing participants and their doctors to make more informed decisions about treatment, including participation in gene-specific clinical trials.

Additional key findings from the PD GENEration study include: brain include:

• 7.7% of participants had GBA1 gene mutations, 2.1% had PRKN gene mutations, and 2.4% had LRRK2 gene mutations. All participants were informed about their genetic status through the program's genetic counseling.
• The prevalence of the gene mutation was significantly higher in high-risk individuals: 18% of those with early onset of Parkinson's disease, high-risk ancestry (such as Ashkenazi Jews, Spanish Basques, or North African Berbers), or a first-degree relative with the disease. The prevalence was nearly 10% in individuals without any of these risk factors.

• Many of these participants may be candidates for precision medicine trials, demonstrating the feasibility and importance of making genetic testing widely available.

We did not expect the high rate of gene mutation positivity, especially the nearly 10% positive results in the absence of known genetic risk factors. Furthermore, the rapidity with which participants were enrolled in PD GENEration is a testament to the interest of PD patients in obtaining data on their genetic status. The positivity rate, combined with the high interest in genotyping, is expected to increase enrollment in observational studies and clinical trials of therapies targeting these genes, streamlining precision medicine clinical trials in PD.

Roy Alkalay, MD, MSc, Associate Professor of Neurology, Columbia University Irving Medical Center

“PD GENEration is at the forefront of the possibilities of precision medicine and personalized treatments, in large part because the Parkinson's Disease Foundation recognized the importance of including genetic counseling in research studies that disclose genetic results,” said Laura Cook, MS, CGC, of ​​the Indiana University School of Medicine's Department of Molecular Genetics and first author of the study. brain The article's author, one of six genetic counselors involved in the study to date, said: “As the study's participant numbers and findings indicate, there is strong interest among people with Parkinson's to further research. This includes understanding the genetics of the disease, both generally and individually. The idea is that we all play our part towards improving treatments and cures.”

PD GENEration is moving to its next phase with support from the Global Parkinson's Genetics Program (GP2), a program of the ASAP (Aligning Science Across Parkinson's) initiative. ASAP funding will enable the Parkinson's Foundation to accelerate the impact of the study by focusing on populations that have historically been underrepresented in research. This large-scale recruitment boost is reaching larger, more diverse communities in the U.S., Canada and Latin America. The Parkinson's Foundation aims to enroll an additional 8,000 participants in the next phase of the study, including 2,400 in Latin America.

“PD GENEration is designed to be inclusive and accessible to all, with the goal of improving clinical outcomes for all. We are proud that the data we have collected through PD GENEration reflects the largest and most diverse North American cohort ever tested. We met our initial recruitment goal of 15,000 participants this spring, but an even bigger goal is on the horizon,” said James Beck, PhD, senior vice president and chief scientific officer at the Parkinson's Disease Foundation. “Our partnership with ASAP and GP2 will enable us to reach much more people and increase participant diversity even further. Understanding the genes common to PD patients across different populations could unlock secrets to the biology of the disease and lead to new treatments.”