Category: Parkinson's Disease: Genetics
Objective: To describe genetic testing results of major genes for Parkinson’s disease (PD) in a North American cohort as part of PD GENEration
Background: Although seven genes (LRRK2, GBA1, PRKN, PINK1, SNCA, PARK7 and VPS35) are established as causative for PD, people with PD (PwP) are often unaware of their genetic status since clinical testing is rarely offered. This limits multiple opportunities, including integrating genetics into clinical care and enrolling PwP into precision medicine trials that recruit only individuals with variants. Furthermore, the yield of genetic testing to inform clinicians is not known in a large North American population.
Method: PD GENEration is a multi-center, observational study, offering genetic testing and counseling to those with PD in the United States, including Puerto Rico; Canada; and the Dominican Republic. DNA samples are analyzed by next-generation sequencing and deletion/duplication analysis (CLIA-certified; Fulgent Genetics). Variants classified as pathogenic/likely pathogenic and clinically actionable are disclosed to participants. Demographic and clinical features are collected at baseline visits.
Results: From September 2019 to January 2023 the study enrolled >7,500 participants across 35 sites and approximately 60 referral centers, with 6,328 tested. Study population characteristics were: 59% male; 90% White, 2% Asian, 2% Black/African American, 9% Hispanic/Latino; mean age of 66.4 ± 10.3 years. Sixteen percent had early-onset PD (age < 50 years), 15% were of high-risk ancestry (Ashkenazi Jewish, Spanish Basque, or North African Berber), and 22% had a first-degree relative with diagnosed PD. Of individuals tested, 842 (13.3%) had a reportable variant; 7.9% with variants in GBA1; 2.4% in LRRK2; 2.2% in PRKN; 0.1% in SNCA; and 0.1% in VPS35, PINK1, or PARK7. Twenty-seven (0.4%) participants had reportable variants in more than one gene.
Conclusion: Genetic testing of well-established PD genes in this cohort resulted in a genetic diagnostic yield of 13.3%, overall, and, notably, 9.2%, in those unsuspected of harboring variants. Together with the increasing utility of self-knowledge of PD gene status, the findings support a shift to offering universal genetic testing to PwP.
To cite this abstract in AMA style:
L. Cook, J. Verbrugge, T. Schwantes-An, T. Foroud, A. Hall, K. Marder, I. Mata, N. Mencacci, M. Nance, M. Schwarzschild, T. Simuni, A-M. Wills, S. Rao, K. Ghosh Galvelis, A. Naito, J. Beck, R. Alcalay. Informing people with Parkinson’s disease of their gene variant status: PD GENEration, a North American observational and registry study [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/informing-people-with-parkinsons-disease-of-their-gene-variant-status-pd-generation-a-north-american-observational-and-registry-study/. Accessed May 17, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/informing-people-with-parkinsons-disease-of-their-gene-variant-status-pd-generation-a-north-american-observational-and-registry-study/