PD GENEration Study Identifies Link Between Genetic Variants, Risk Factors, and Parkinson Disease

Thirteen percent of participants in the ongoing PD GENEration clinical study (NCT04057794, NCT04994015) possess reportable genetic variants in 7 genes that were previously adjudicated by the ClinGen Parkinson’s Disease Gene Curation Expert Panel (PD GCEP) as being causally linked to Parkinson disease (PD). Reportable variants were most frequently observed in the GBA1 and LRRK2 genes and were associated with risk factors including earlier age at onset (AAO), having first-degree family history of PD, or having high-risk ancestries (Askhkenazi Jewish/Basque/North African Berber). The findings, which were published in Brain, highlight the importance of genetic testing for PD.

PD-GENEration is an ongoing, observational studying that enrolled 10,510 participants from over 85 centers between 2019 to 2023, with results disclosed and genetic counseling provided to all participants from the United States, Canada, and the Dominican Republic. Of the enrolled population, 8301 participants completed testing and received results as of June 1, 2023.

In terms of risk factors among these participants:

• 16% had early onset disease (age <50 years)
• 20% had a first-degree relative with PD
• 14% had high-risk ancestry

Results demonstrate an overall yield of reportable genetic variants in 13% of unselected enrolled participants.

• Variants in GBA1 were found in 7.7% of participants.
• LRRK2, 2.4%.
• PKKN, 2.1%
• SNCA, 0.1%
• PINK1, PARK7, or VPS35 combined, 0.2%

Additionally, 18% of participants with high risk factors possessed genetic variants, while there was a 9% yield for participants without these risk factors.