Objective:

Provide clinical whole genome sequencing (WGS) and genetic counseling to a diverse and international population of people living with Parkinson’s disease (PD).

Background:

The PD GENEration study (NCT04994015), sponsored by the Parkinson's Foundation in partnership with the Global Parkinson’s Genetics Program (GP2), now offers WGS with genetic counseling and return of results to broad populations of people living with PD (PwP) in over 8 countries in the Americas and Israel. Testing includes a panel of 7 PD associated genes linked to parkinsonism and an additional 21 genes that may be linked to parkinsonisms or Parkinson’s disease.

Design/Methods:

In preparation for providing WGS and genetic counseling internationally, PD GENEration partnered with a multi-center collaboration across Latin America (the Latin American Research consortium on the GEnetics of Parkinson's Disease – LARGE-PD), connected with sites in Canada and Israel, and adapted genetic counseling materials developed in the US in English and Spanish for use in other jurisdictions, taking into account each country’s infrastructure, cultural differences and genetic counseling training needs. A decentralized study model and “train the trainer” methods allowed PD GENEration to interact with other international PD genetics efforts to expand its work internationally.

Results:

As of October 8, 2024, 1837 participants have enrolled into WGS testing as part of an overall cohort of more than 18,000 PWP enrolled since 2019. The positivity rate of the entire cohort was 12.2%, comprising GBA1 (7.4%), LRRK2 (2.4%), and PRKN (2.4%) pathogenic variants. All genomic sequencing and clinical data will be publicly available through the AMP-PD program.

Conclusions:

Providing clinical genetic results to an increasingly diverse and international cohort of PwP and their clinicians furthers our goals of: 1) Expanding our understanding of the complex genetics underlying PD, and 2) Facilitating the design and execution of precision medicine trials in PD.