Abstract
Background: Until recently, about three-quarters of all monogenic Parkinson's disease (PD) studies were performed in European/White ancestry, thereby severely limiting our insights into genotype–phenotype relationships at a global scale. Objective: To identify the multi-ancestry spectrum of monogenic PD. Methods: The first systematic approach to embrace monogenic PD worldwide, The Michael J. Fox Foundation Global Monogenic PD Project, contacted authors of publications reporting individuals carrying pathogenic variants in known PD-causing genes. In contrast, the Global Parkinson's Genetics Program's Monogenic Network took a different approach by targeting PD centers underrepresented or not yet represented in the medical literature. Results: In this article, we describe combining both efforts in a merger project resulting in a global monogenic PD cohort with the buildup of a sustainable infrastructure to identify the multi-ancestry spectrum of monogenic PD and enable studies of factors modifying penetrance and expressivity of monogenic PD. Conclusions: This effort demonstrates the value of future research based on team science approaches to generate comprehensive and globally relevant results.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1868-1873 |
| Number of pages | 6 |
| Journal | Movement Disorders |
| Volume | 39 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2024 |
Funding
Niccol\u00F2 E. Mencacci is supported by the NIH (1K08NS131581) and the ASAP GP2; is a member of the steering committee of the PD GENEration study; and receives an honorarium from the Parkinson's Foundation. Thomas Gasser has received a grant and a Steering Committee Member Award from MJFF; has received a grant from the Bundesministerium fuer Bildung und Forschung (BMBF) and the Deutsche Forschungsgemeinschaft (DFG); has received speakers\u2019 honoraria from UCB Pharma, Novartis, Teva, and MedUpdate; has received consulting fees from Bayer AG, Blue Rock Therapeutics, and Coave Therapeutics; and is chairman of the scientific advisory board of the \u201CJoint Programming for Neurodegenerative Diseases,\u201D funded by the European Commission. Ignacio F. Mata is supported by MJFF, the ASAP GP2, and the National Institutes of Health (NIH; R01NS112499), and is also a member of the steering committee of the PD GENEration study. Kishore R. Kumar is supported by the ASAP GP2; receives research funding from the Paul Ainsworth Family Foundation and Medical Research Future Fund (Grants 2023126, 2023357, and 2024888); and receives honorarium for lecturing from the International Parkinson and Movement Disorder Society, unrelated to the current manuscript. Joanne Trinh is funded by the DFG and Else Kr\u00F6ner\u2010Fresenius\u2010Stiftung (EKFS). This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging, Department of Health and Human Services (project no. ZO1 AG000534), as well as the National Institute of Neurological Disorders and Stroke. Global Parkinson's Genetics Program was supported by the Aligning Science Across Parkinson's initiative and implemented by The Michael J. Fox Foundation for Parkinson's Research ( https://gp2.org ). Funding agencies: Enza Maria Valente is supported by the ASAP GP2 and has received research grants from the Italian Ministry of Health, Telethon Foundation Italy, and Cariplo Foundation Italy. Katja Lohmann is supported by the German Research Foundation. J.J. has received a Family Mobility Grant from the University of Luebeck. L.M.L., E.\u2010J.V., A.A.A., M.A., S.B., C.G., P.H., A.I., S.P., J.S., J.T., and K.L. have nothing to report. K.R. was supported by the Global Parkinson's Genetics Program (GP2) funded by the Align Science Across Parkinson's (ASAP) initiative and implemented by The Michael J. Fox Foundation (MJFF). M.L.M.D. was supported by the GP2 funded by the ASAP initiative and implemented by MJFF. N.B. has received salary support from GP2. M.E. was supported by the ASAP GP2. T.G. received a grant and a Steering Committee Member Award from MJFF. Y.K. has received salary support from GP2. I.J.K.S. was supported by the ASAP GP2. K.R.K. was supported by the ASAP GP2. S.\u2010Y.L. reported consultancies from MJFF and research grants from MJFF. H.M. has received salary support as part of his involvement with the GP2, an initiative under the ASAP umbrella; this support was provided by MJFF. I.F.M. was supported by MJFF, the ASAP GP2, and the National Institutes of Health (NIH; R01NS112499) and was also a member of the steering committee of the PD GENEration study. N.E.M. was supported by the ASAP GP2 and was a member of the steering committee of the PD GENEration study. M.A.N.'s participation in this project was part of a competitive contract awarded to DataTecnica LLC by the NIH to support open science research. C.S. was supported by the GP2 funded by the ASAP initiative and implemented by MJFF. A.\u2010H.T. received research support from MJFF. E.M.V. was supported by the ASAP GP2. A.S. was supported by the ASAP GP2. C.B. was supported by the ASAP GP2. Zih\u2010Hua Fang was supported by the ASAP GP2 and has received GP2 salary support from MJFF. C.K. served as a medical advisor to Centogene, Takeda, and Retromer Therapeutics; has received speakers' honoraria from Bial and Desitin; and was supported by the ASAP GP2. Relevant conflicts of interest/financial disclosures: Soraya Bardien is supported by the National Research Foundation of South Africa. Mike A. Nalls's participation in this project was part of a competitive contract awarded to DataTecnica LLC by the NIH to support open science research; he also currently serves on the scientific advisory board for Character Bio Inc. and is a scientific founder at Neuron23 Inc.
Keywords
- GP2
- MJFF GMPD
- Parkinson's disease
- monogenic Parkinson's disease
- parkinsonism
ASJC Scopus subject areas
- Neurology
- Clinical Neurology