Category: Parkinson's Disease: Genetics
Objective: To create a global cohort of manifesting and non-manifesting carriers of pathogenic variants in known monogenic Parkinson’s disease (PD) genes, such as LRRK2, PRKN, and PINK1, to better understand the phenotypic and genotypic spectrum in diverse populations, and to identify genetic modifiers of penetrance and expressivity through a genome-wide association study (GWAS) approach.
Background: The Michael J Fox Foundation Global Genetic Parkinson’s Disease (MJFF GGPD) project uses a clinicians’ and scientists’ global science team approach to identify monogenic forms of PD worldwide [1]. The Monogenic Hub (https://monogenic.gp2.org/) of the Global Parkinson’s Genetics Program (GP2) aims to identify genetic causes in suspected monogenic PD [2].
Method: Four target groups were created depending on their participation in either or both projects: 1) members of GP2 monogenic hub and MJFF GGPD project, 2) members of MJFF GGPD project that have submitted data and DNA samples, 3) members of the MJFF GGPD project that have submitted data only, and 4) members of GP2 monogenic hub. Each group received a customized email communicating the relevant information about the merger and an online survey. The online survey requested information such as an agreement with the merger, interest in joining GP2, and availability of DNA samples of monogenic PD carriers.
Results: 167 emails were sent to 118 centers in 50 countries. We have currently received 83 email responses (~50%), and 58 online surveys have been completed. Based on the responses from the online survey, approximately 3000 samples of known monogenic PD are available, with 100% of collaborators who responded, in agreement with the merger and expressing interest in participating in the GP2 Monogenic Hub.
Conclusion: With the merger of the two projects all 89 MJFF GGPD centers and/or GP2 Monogenic Hub sites in 50 countries can contribute clinical data and DNA samples of known monogenic PD patients and their families to this effort. The integration of the MJFF GGPD project into the GP2 Monogenic Hub will massively increase the power to investigate modifiers of known monogenic PD worldwide and thus enables meaningful, population-specific genotype-phenotype relationships.
References: [1] Vollstedt EJ, Kasten M, Klein C; MJFF Global Genetic Parkinson’s Disease Study Group. Using global team science to identify genetic Parkinson’s disease worldwide. Ann Neurol. 2019 Aug;86(2):153-157. DOI: 10.1002/ana.25514. Epub 2019 Jun 26. PMID: 31155756; PMCID: PMC7410260. [2] The Global Parkinson’s Genetics Program. GP2: The Global Parkinson’s Genetics Program. Mov Disord. First published: Jan 29, 2021. https://doi.org/10.1002/mds.28494.
To cite this abstract in AMA style:
K. Roopnarain, E. Vollstedt,, L. Lange, S. Padmanabhan, C. Blauwendraat, A. Singleton, K. Katja, C. Klein. Merging global cohorts of manifesting and non-manifesting carriers of pathogenic variants in known Parkinson’s disease genes [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/merging-global-cohorts-of-manifesting-and-non-manifesting-carriers-of-pathogenic-variants-in-known-parkinsons-disease-genes/. Accessed June 15, 2025.« Back to 2022 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/merging-global-cohorts-of-manifesting-and-non-manifesting-carriers-of-pathogenic-variants-in-known-parkinsons-disease-genes/