Category: Parkinson's Disease: Genetics
Objective: To provide secondary health findings (SHF) results to participants enrolled in the PD GENEration study via CLIA genetic testing using whole genome sequencing (WGS) with disclosure of 21 genes linked to parkinsonism or Parkinson’s disease (PD) and 10 non-PD related genes to people with PD (PwP) globally (Fig. 1).
Background: The PD GENEration study (NCT04994015), sponsored by the Parkinson’s Foundation with support of the Global Parkinson’s Genetics Program (GP2), has provided genetic testing and counseling for seven PD related genes to 22,000+ PwP. In 2024, the study transitioned to WGS from targeted exome sequencing, opening the door for return of results (ROR) beyond the primary seven gene panel.
Method: Rare variants in secondary PD-related genes were formally evaluated by GP2 and the PD GENEration team and two gene panels were designed. One panel captures 21 genes linked to parkinsonism, PD or PD mimickers and the other focuses on non-PD related genes known as the CDC-10 Tier 1 genes (e.g., BRCA1). Participants can consent to receive results from one or both new panels during genetic counseling for the results of the primary panel.
Results: In Nov 2024, participants began to receive SHF results. As of Feb 2025, 5041 participants consented to receive SHF (96% of participants with WGS). Of those, genetic testing has been completed for 506 (10%) participants, of which 24 (5%) were positive for genetic variation on the expanded parkinsonism panel and 2 (0.4%) were positive for genetic variation on the CDC-10 Tier 1 panel. Gene specific counseling strategies and fact sheets were developed to align with the established workflow used for the primary seven gene panel.
Conclusion: A flexible framework has been created for the implementation and return of results of SHF to participants. This flexibility allows for the periodic re-evaluation of genes for SHF panels to remain current with clinical genetic literature. Future studies will test the impact, satisfaction or regret of PwP receiving positive results from these panels.
Primary and Secondary Panels
To cite this abstract in AMA style:
M. Dini, K. Ghosh Galvelis, N. Bothwick, L. Caboy, M. Caulfield, R. de Leon, A. Dilliott, I. Khaderi, S. Rao, A. Yake, A. Coral Zambrano, R. Bhisetti, S. Lawrence, S. Li, Y. Lu, U. Ragunathan, T. Foroud, V. Caceres, L. Cook, K. Fiallos, L. Heathers, R. Hodges, A. Miller, A. Neibaur, M. Rumbaugh, M. Totten, J. Verbrugge, A. Hall, K. Marder, I. Mata, N. Mencacci, M. Nance, T. Simuni, M. Schwarzschild, A. Wills, H. Gao, C. Blauwendraat, J. Beck, R. Alcalay. Returning Secondary Health Findings in the PD GENEration study [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/returning-secondary-health-findings-in-the-pd-generation-study/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/returning-secondary-health-findings-in-the-pd-generation-study/