. 2024 Oct;39(10):1868-1873.

doi: 10.1002/mds.29925. Epub 2024 Jul 30.

Team Science Approaches to Unravel Monogenic Parkinson's Disease on a Global Scale

Johanna Junker^{1

2}, Lara M Lange^{1

2}, Eva-Juliane Vollstedt¹, Karisha Roopnarain³, Maria Leila M Doquenia¹, Azlina Ahmad Annuar⁴, Micol Avenali^{5

6}, Soraya Bardien^{7

8}, Natascha Bahr¹, Melina Ellis^{9

10}, Caterina Galandra^{5

11}, Thomas Gasser^{12

13}, Peter Heutink^{12

13}, Anastasia Illarionova¹³, Yuliia Kanana¹, Ignacio J Keller Sarmiento¹⁴, Kishore R Kumar^{10

15

16}, Shen-Yang Lim¹⁷, Harutyun Madoev¹, Ignacio F Mata¹⁸, Niccolò E Mencacci¹⁴, Mike A Nalls^{19

20}, Shalini Padmanabhan²¹, Cholpon Shambetova¹, J C Solle²², Ai-Huey Tan¹⁷, Joanne Trinh¹, Enza Maria Valente^{6

11}, Andrew Singleton^{20

23}, Cornelis Blauwendraat^{20

23}, Katja Lohmann¹, Zih-Hua Fang¹³, Christine Klein¹; Global Parkinson's Genetics Program (GP2)

Collaborators, Affiliations

Collaborators

Affiliations

¹ Institute of Neurogenetics, University of Luebeck, Luebeck, Germany.
² Department of Neurology, University Clinic Schleswig-Holstein, Luebeck, Germany.
³ Department of Neurology, University of Free State, Bloemfontein, South Africa.
⁴ Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁵ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
⁶ IRCCS Mondino Foundation, Pavia, Italy.
⁷ Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
⁸ South African Medical Research Council/Stellenbosch University Genomics of Brain Disorders Research Unit, Stellenbosch University, Cape Town, South Africa.
⁹ Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, New South Wales, Australia.
¹⁰ Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
¹¹ Department of Molecular Medicine, University of Pavia, Pavia, Italy.
¹² Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
¹³ German Center for Neurodegenerative Diseases, Tuebingen, Germany.
¹⁴ Ken and Ruth Davee Department of Neurology and Simpson Querrey Center for Neurogenetics, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁵ Translational Neurogenomics, Genomic and Inherited Disease Program, Garvan Institute of Medical Research and UNSW Sydney, Darlinghurst, New South Wales, Australia.
¹⁶ Molecular Medicine Laboratory and Neurology Department, Concord Repatriation General Hospital, The University of Sydney, Concord, New South Wales, Australia.
¹⁷ Division of Neurology, Department of Medicine, and the Mah Pooi Soo and Tan Chin Nam Centre for Parkinson's and Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
¹⁸ Genomic Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁹ DataTecnica, Washington, DC, USA.
²⁰ Center for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
²¹ Discovery and Translational Research, The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
²² Department of Clinical Research, The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
²³ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.

PMID: 39076159
PMCID: PMC12131278
DOI: 10.1002/mds.29925

Team Science Approaches to Unravel Monogenic Parkinson's Disease on a Global Scale

Johanna Junker et al. Mov Disord. 2024 Oct.

. 2024 Oct;39(10):1868-1873.

doi: 10.1002/mds.29925. Epub 2024 Jul 30.

Authors

Collaborators

Affiliations

¹ Institute of Neurogenetics, University of Luebeck, Luebeck, Germany.
² Department of Neurology, University Clinic Schleswig-Holstein, Luebeck, Germany.
³ Department of Neurology, University of Free State, Bloemfontein, South Africa.
⁴ Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁵ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
⁶ IRCCS Mondino Foundation, Pavia, Italy.
⁷ Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
⁸ South African Medical Research Council/Stellenbosch University Genomics of Brain Disorders Research Unit, Stellenbosch University, Cape Town, South Africa.
⁹ Northcott Neuroscience Laboratory, ANZAC Research Institute, Concord, New South Wales, Australia.
¹⁰ Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
¹¹ Department of Molecular Medicine, University of Pavia, Pavia, Italy.
¹² Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.
¹³ German Center for Neurodegenerative Diseases, Tuebingen, Germany.
¹⁴ Ken and Ruth Davee Department of Neurology and Simpson Querrey Center for Neurogenetics, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁵ Translational Neurogenomics, Genomic and Inherited Disease Program, Garvan Institute of Medical Research and UNSW Sydney, Darlinghurst, New South Wales, Australia.
¹⁶ Molecular Medicine Laboratory and Neurology Department, Concord Repatriation General Hospital, The University of Sydney, Concord, New South Wales, Australia.
¹⁷ Division of Neurology, Department of Medicine, and the Mah Pooi Soo and Tan Chin Nam Centre for Parkinson's and Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
¹⁸ Genomic Medicine Institute, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁹ DataTecnica, Washington, DC, USA.
²⁰ Center for Alzheimer's and Related Dementias, National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
²¹ Discovery and Translational Research, The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
²² Department of Clinical Research, The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
²³ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.

PMID: 39076159
PMCID: PMC12131278
DOI: 10.1002/mds.29925

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. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: GP2; MJFF GMPD; Parkinson's disease; monogenic Parkinson's disease; parkinsonism.

PubMed Disclaimer

Conflict of interest statement

J.J. has received a Family Mobility Grant from the University of Luebeck. L.M.L., E.-J.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.-Y.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.-H.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-Hua 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.

Figures

**FIG. 1.**
World map of centers participating in the Global Parkinson’s Genetics Program’s Monogenic Network (GP2’s MN) and The Michael J. Fox Foundation Global Monogenic PD (MJFF GMPD) project. Colored are the countries from which one or more centers participated in The MJFF GMPD project and GP2’s MN (blue) or only in GP2’s MN (green). Colored in purple are new centers in underrepresented countries that were recruited based on the new approach of GP2’s MN. Blue: Argentina, Australia, Austria, Belgium, Canada, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Luxembourg, Malaysia, Netherlands, Norway, Poland, Portugal, Saudi Arabia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, and United States. Green: Chile, Czechia, New Zealand, and Switzerland. Purple: Bangladesh, Colombia, Indonesia, Iran, Mongolia, Nepal, Nigeria, Pakistan, Philippines, Sri Lanka, and Tunisia.

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Update of

Understanding monogenic Parkinson's disease at a global scale.
Junker J, Lange LM, Vollstedt EJ, Roopnarain K, Doquenia MLM, Annuar AA, Avenali M, Bardien S, Bahr N, Ellis M, Galandra C, Gasser T, Heutink P, Illarionova A, Kanana Y, Keller Sarmiento IJ, Kumar KR, Lim SY, Madoev H, Mata IF, Mencacci NE, Nalls MA, Padmanabhan S, Shambetova C, Solle J, Tan AH, Trinh J, Valente EM, Singleton A, Blauwendraat C, Lohmann K, Fang ZH, Klein C; Global Parkinson’s Genetics Program (GP2). Junker J, et al. medRxiv [Preprint]. 2024 Apr 9:2024.03.12.24304154. doi: 10.1101/2024.03.12.24304154. medRxiv. 2024. Update in: Mov Disord. 2024 Oct;39(10):1868-1873. doi: 10.1002/mds.29925. PMID: 38529492 Free PMC article. Updated. Preprint.

References

1. Vollstedt EJ, Schaake S, Lohmann K, et al. Embracing monogenic Parkinson’s disease: the MJFF global genetic PD cohort. Mov Disord 2023;38(2):286–303. - PubMed
1. Schiess N, Cataldi R, Okun MS, et al. Six action steps to address global disparities in Parkinson disease: a World Health Organization priority. JAMA Neurol 2022;79(9):929–936. - PubMed
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1. Trinh J, Zeldenrust FMJ, Huang J, et al. Genotype-phenotype relations for the Parkinson’s disease genes SNCA, LRRK2, VPS35: MDSGene systematic review. Mov Disord 2018;33(12):1857–1870. - PubMed
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Team Science Approaches to Unravel Monogenic Parkinson's Disease on a Global Scale

Collaborators

Affiliations

Team Science Approaches to Unravel Monogenic Parkinson's Disease on a Global Scale

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

Update of

References

MeSH terms

Grants and funding

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Medical