Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

Clodagh Towns¹, Madeleine Richer¹, Simona Jasaityte¹, Eleanor J Stafford^{1

2}, Julie Joubert¹, Tarek Antar³, Alejandro Martinez-Carrasco^{1

2}, Mary B Makarious^{1

3

4}, Bradford Casey^{5

6}, Dan Vitale^{4

7

8}, Kristin Levine^{7

8}, Hampton Leonard^{3

7

8

9}, Caroline B Pantazis^{4

7}, Laurel A Screven⁷, Dena G Hernandez³, Claire E Wegel¹⁰, Justin Solle⁵, Mike A Nalls^{3

4

7

8}, Cornelis Blauwendraat^{4

7

11}, Andrew B Singleton^{3

7

12}, Manuela M X Tan¹³, Hirotaka Iwaki^{3

7

8}, Huw R Morris^{14

15}; Global Parkinson’s Genetics Program (GP2)

Collaborators, Affiliations

Collaborators

Global Parkinson’s Genetics Program (GP2):
Emilia M Gatto, Marcelo Kauffman, Samson Khachatryan, Zaruhi Tavadyan, Claire E Shepherd, Julie Hunter, Kishore Kumar, Melina Ellis, Miguel E Rentería, Sulev Koks, Alexander Zimprich, Artur F Schumacher-Schuh, Carlos Rieder, Paula Saffie Awad, Vitor Tumas, Sarah Camargos, Edward A Fon, Oury Monchi, Ted Fon, Benjamin Pizarro Galleguillos, Marcelo Miranda, Maria Leonor Bustamante, Patricio Olguin, Pedro Chana, Beisha Tang, Huifang Shang, Jifeng Guo, Piu Chan, Wei Luo, Gonzalo Arboleda, Jorge Orozco, Marlene Jimenez Del Rio, Alvaro Hernandez, Mohamed Salama, Walaa A Kamel, Yared Z Zewde, Alexis Brice, Jean-Christophe Corvol, Ana Westenberger, Anastasia Illarionova, Brit Mollenhauer, Christine Klein, Eva-Juliane Vollstedt, Franziska Hopfner, Günter Höglinger, Harutyun Madoev, Joanne Trinh, Johanna Junker, Katja Lohmann, Lara M Lange, Manu Sharma, Sergiu Groppa, Thomas Gasser, Zih-Hua Fang, Albert Akpalu, Georgia Xiromerisiou, Georgios Hadjigorgiou, Ioannis Dagklis, Ioannis Tarnanas, Leonidas Stefanis, Maria Stamelou, Efthymios Dadiotis, Alex Medina, Germaine Hiu-Fai Chan, Nancy Ip, Nelson Yuk-Fai Cheung, Phillip Chan, Xiaopu Zhou, Asha Kishore, Divya Kp, Pramod Pal, Prashanth Lingappa Kukkle, Roopa Rajan, Rupam Borgohain, Mehri Salari, Andrea Quattrone, Enza Maria Valente, Lucilla Parnetti, Micol Avenali, Tommaso Schirinzi, Manabu Funayama, Nobutaka Hattori, Tomotaka Shiraishi, Altynay Karimova, Gulnaz Kaishibayeva, Cholpon Shambetova, Rejko Krüger, Ai Huey Tan, Azlina Ahmad-Annuar, Mohamed Ibrahim Norlinah, Nor Azian Abdul Murad, Shahrul Azmin, Shen-Yang Lim, Wael Mohamed, Yi Wen Tay, Daniel Martinez-Ramirez, Mayela Rodriguez-Violante, Paula Reyes-Pérez, Bayasgalan Tserensodnom, Rajeev Ojha, Tim J Anderson, Toni L Pitcher, Arinola Sanyaolu, Njideka Okubadejo, Oluwadamilola Ojo, Jan O Aasly, Lasse Pihlstrøm, Manuela Tan, Shoaib Ur-Rehman, Mario Cornejo-Olivas, Maria Leila Doquenia, Raymond Rosales, Angel Vinuela, Elena Iakovenko, Bashayer Al Mubarak, Muhammad Umair, Eng-King Tan, Jia Nee Foo, Ferzana Amod, Jonathan Carr, Soraya Bardien, Beomseok Jeon, Yun Joong Kim, Esther Cubo, Ignacio Alvarez, Janet Hoenicka, Katrin Beyer, Maria Teresa Periñan, Pau Pastor, Sarah El-Sadig, Christiane Zweier, Paul Krack, Chin-Hsien Lin, Hsiu-Chuan Wu, Pin-Jui Kung, Ruey-Meei Wu, Yihru Wu, Rim Amouri, Samia Ben Sassi, A Nazlı Başak, Gencer Genc, Özgür Öztop Çakmak, Sibel Ertan, Alastair Noyce, Anette Schrag, Anthony Schapira, Camille Carroll, Claire Bale, Donald Grosset, Henry Houlden, John Hardy, Kin Ying Mok, Mie Rizig, Nicholas Wood, Nigel Williams, Olaitan Okunoye, Patrick Alfryn Lewis, Rauan Kaiyrzhanov, Rimona Weil, Seth Love, Simon Stott, Simona Jasaitye, Sumit Dey, Vida Obese, Alberto Espay, Alyssa O'Grady, Andrew K Sobering, Bernadette Siddiqi, Brian Fiske, Cabell Jonas, Carlos Cruchaga, Charisse Comart, Claire Wegel, Deborah Hall, Dena Hernandez, Ejaz Shiamim, Ekemini Riley, Faraz Faghri, Geidy E Serrano, Honglei Chen, Ignacio F Mata, Ignacio Juan Keller Sarmiento, Jared Williamson, Jonggeol Jeff Kim, Joseph Jankovic, Joshua Shulman, Justin C Solle, Kaileigh Murphy, Karen Nuytemans, Karl Kieburtz, Katerina Markopoulou, Kenneth Marek, Kristin S Levine, Lana M Chahine, Laura Ibanez, Laurel Screven, Lauren Ruffrage, Lisa Shulman, Luca Marsili, Maggie Kuhl, Marissa Dean, Mathew Koretsky, Megan J Puckelwartz, Miguel Inca-Martinez, Naomi Louie, Niccolò Emanuele Mencacci, Roger Albin, Roy Alcalay, Ruth Walker, Sara Bandres-Ciga, Sohini Chowdhury, Sonya Dumanis, Steven Lubbe, Tao Xie, Tatiana Foroud, Thomas Beach, Todd Sherer, Yeajin Song, Duan Nguyen, Toan Nguyen, Masharip Atadzhanov

Affiliations

¹ Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.
² University College London, London, UK.
³ Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
⁴ National Institutes of Health, Bethesda, MD, USA.
⁵ Department of Clinical Research, Michael J. Fox Foundation for Parkinson's Research, New York City, NY, USA.
⁶ The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA.
⁷ Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
⁸ Data Tecnica International, Washington, DC, USA.
⁹ National Institute on Aging/National Institutes of Health, Bethesda, MD, USA.
¹⁰ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
¹¹ Integrative Genomics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
¹² National Institute on Aging, Bethesda, MD, USA.
¹³ Department of Neurology, Oslo University Hospital, Oslo, Norway.
¹⁴ Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK. h.morris@ucl.ac.uk.
¹⁵ University College London, London, UK. h.morris@ucl.ac.uk.

PMID: 37699923
PMCID: PMC10497609
DOI: 10.1038/s41531-023-00533-w

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

Clodagh Towns et al. NPJ Parkinsons Dis. 2023.

. 2023 Sep 12;9(1):131.

doi: 10.1038/s41531-023-00533-w.

Authors

Collaborators

Global Parkinson’s Genetics Program (GP2):
Emilia M Gatto, Marcelo Kauffman, Samson Khachatryan, Zaruhi Tavadyan, Claire E Shepherd, Julie Hunter, Kishore Kumar, Melina Ellis, Miguel E Rentería, Sulev Koks, Alexander Zimprich, Artur F Schumacher-Schuh, Carlos Rieder, Paula Saffie Awad, Vitor Tumas, Sarah Camargos, Edward A Fon, Oury Monchi, Ted Fon, Benjamin Pizarro Galleguillos, Marcelo Miranda, Maria Leonor Bustamante, Patricio Olguin, Pedro Chana, Beisha Tang, Huifang Shang, Jifeng Guo, Piu Chan, Wei Luo, Gonzalo Arboleda, Jorge Orozco, Marlene Jimenez Del Rio, Alvaro Hernandez, Mohamed Salama, Walaa A Kamel, Yared Z Zewde, Alexis Brice, Jean-Christophe Corvol, Ana Westenberger, Anastasia Illarionova, Brit Mollenhauer, Christine Klein, Eva-Juliane Vollstedt, Franziska Hopfner, Günter Höglinger, Harutyun Madoev, Joanne Trinh, Johanna Junker, Katja Lohmann, Lara M Lange, Manu Sharma, Sergiu Groppa, Thomas Gasser, Zih-Hua Fang, Albert Akpalu, Georgia Xiromerisiou, Georgios Hadjigorgiou, Ioannis Dagklis, Ioannis Tarnanas, Leonidas Stefanis, Maria Stamelou, Efthymios Dadiotis, Alex Medina, Germaine Hiu-Fai Chan, Nancy Ip, Nelson Yuk-Fai Cheung, Phillip Chan, Xiaopu Zhou, Asha Kishore, Divya Kp, Pramod Pal, Prashanth Lingappa Kukkle, Roopa Rajan, Rupam Borgohain, Mehri Salari, Andrea Quattrone, Enza Maria Valente, Lucilla Parnetti, Micol Avenali, Tommaso Schirinzi, Manabu Funayama, Nobutaka Hattori, Tomotaka Shiraishi, Altynay Karimova, Gulnaz Kaishibayeva, Cholpon Shambetova, Rejko Krüger, Ai Huey Tan, Azlina Ahmad-Annuar, Mohamed Ibrahim Norlinah, Nor Azian Abdul Murad, Shahrul Azmin, Shen-Yang Lim, Wael Mohamed, Yi Wen Tay, Daniel Martinez-Ramirez, Mayela Rodriguez-Violante, Paula Reyes-Pérez, Bayasgalan Tserensodnom, Rajeev Ojha, Tim J Anderson, Toni L Pitcher, Arinola Sanyaolu, Njideka Okubadejo, Oluwadamilola Ojo, Jan O Aasly, Lasse Pihlstrøm, Manuela Tan, Shoaib Ur-Rehman, Mario Cornejo-Olivas, Maria Leila Doquenia, Raymond Rosales, Angel Vinuela, Elena Iakovenko, Bashayer Al Mubarak, Muhammad Umair, Eng-King Tan, Jia Nee Foo, Ferzana Amod, Jonathan Carr, Soraya Bardien, Beomseok Jeon, Yun Joong Kim, Esther Cubo, Ignacio Alvarez, Janet Hoenicka, Katrin Beyer, Maria Teresa Periñan, Pau Pastor, Sarah El-Sadig, Christiane Zweier, Paul Krack, Chin-Hsien Lin, Hsiu-Chuan Wu, Pin-Jui Kung, Ruey-Meei Wu, Yihru Wu, Rim Amouri, Samia Ben Sassi, A Nazlı Başak, Gencer Genc, Özgür Öztop Çakmak, Sibel Ertan, Alastair Noyce, Anette Schrag, Anthony Schapira, Camille Carroll, Claire Bale, Donald Grosset, Henry Houlden, John Hardy, Kin Ying Mok, Mie Rizig, Nicholas Wood, Nigel Williams, Olaitan Okunoye, Patrick Alfryn Lewis, Rauan Kaiyrzhanov, Rimona Weil, Seth Love, Simon Stott, Simona Jasaitye, Sumit Dey, Vida Obese, Alberto Espay, Alyssa O'Grady, Andrew K Sobering, Bernadette Siddiqi, Brian Fiske, Cabell Jonas, Carlos Cruchaga, Charisse Comart, Claire Wegel, Deborah Hall, Dena Hernandez, Ejaz Shiamim, Ekemini Riley, Faraz Faghri, Geidy E Serrano, Honglei Chen, Ignacio F Mata, Ignacio Juan Keller Sarmiento, Jared Williamson, Jonggeol Jeff Kim, Joseph Jankovic, Joshua Shulman, Justin C Solle, Kaileigh Murphy, Karen Nuytemans, Karl Kieburtz, Katerina Markopoulou, Kenneth Marek, Kristin S Levine, Lana M Chahine, Laura Ibanez, Laurel Screven, Lauren Ruffrage, Lisa Shulman, Luca Marsili, Maggie Kuhl, Marissa Dean, Mathew Koretsky, Megan J Puckelwartz, Miguel Inca-Martinez, Naomi Louie, Niccolò Emanuele Mencacci, Roger Albin, Roy Alcalay, Ruth Walker, Sara Bandres-Ciga, Sohini Chowdhury, Sonya Dumanis, Steven Lubbe, Tao Xie, Tatiana Foroud, Thomas Beach, Todd Sherer, Yeajin Song, Duan Nguyen, Toan Nguyen, Masharip Atadzhanov

Affiliations

¹ Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK.
² University College London, London, UK.
³ Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
⁴ National Institutes of Health, Bethesda, MD, USA.
⁵ Department of Clinical Research, Michael J. Fox Foundation for Parkinson's Research, New York City, NY, USA.
⁶ The Michael J. Fox Foundation for Parkinson's Research, New York, NY, USA.
⁷ Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
⁸ Data Tecnica International, Washington, DC, USA.
⁹ National Institute on Aging/National Institutes of Health, Bethesda, MD, USA.
¹⁰ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
¹¹ Integrative Genomics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
¹² National Institute on Aging, Bethesda, MD, USA.
¹³ Department of Neurology, Oslo University Hospital, Oslo, Norway.
¹⁴ Department of Clinical and Movement Neurosciences, Queen Square Institute of Neurology, University College London, London, UK. h.morris@ucl.ac.uk.
¹⁵ University College London, London, UK. h.morris@ucl.ac.uk.

PMID: 37699923
PMCID: PMC10497609
DOI: 10.1038/s41531-023-00533-w

Abstract

The Global Parkinson's Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia.

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Conflict of interest statement

A.B.S. and C.B. are supported by the Intramural Research Program of the National Institute on Aging and have received grant support from the Michael J. Fox Foundation for Parkinson’s Research and the Aligning Science Across Parkinson’s Initiative. A.B.S. has received royalty payments related to a diagnostic for stroke. A.B.S. is an editor for npj Parkinson’s Disease. A.B.S. was not involved in the journal’s review of, or decisions related to, this manuscript. H.L., H.I., D.V., K.L., and M.A.N. are consultants employed by Data Tecnica International. Data Tecnica is engaged in a consulting agreement with the US National Institutes of Health. H.R.M. is employed by UCL. In the last 24 months, he reports paid consultancy from Biogen, Biohaven, Lundbeck; lecture fees/honoraria from Wellcome Trust, Movement Disorders Society; Research Grants from Parkinson’s UK, Cure Parkinson’s Trust, PSP Association, CBD Solutions, Drake Foundation, Medical Research Council, Michael J. Fox Foundation. H.R.M. is also a co-applicant on a patent application related to C9ORF72—Method for diagnosing a neurodegenerative disease (PCT/GB2012/052140). BC and JS are employed by the Michael J. Fox Foundation for Parkinson’s Research. All other authors declare no financial or non-financial competing interests.

Figures

**Fig. 1. Cohort integration workflow.**
Data are contributed and returned to the local PI (green); new genetic data, data cleaning and harmonization are carried out by GP2 and made available for analysis within the GP2 consortium (blue); and data are released to qualified investigators via AMP-PD (orange). AMP-PD Accelerating Medicines Partnership - Parkinson’s Disease (https://amp-pd.org).

See this image and copyright information in PMC

References

1. Nalls MA, et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 2019;18:1091–1102. doi: 10.1016/S1474-4422(19)30320-5. - DOI - PMC - PubMed
1. Iwaki H, et al. Genetic risk of Parkinson disease and progression: an analysis of 13 longitudinal cohorts. Neurol. Genet. 2019;5:1–14. doi: 10.1212/NXG.0000000000000348. - DOI - PMC - PubMed
1. Latourelle JC, et al. Large-scale identification of clinical and genetic predictors of Parkinson’s disease motor progression in newly-diagnosed patients: a longitudinal cohort study and validation. Lancet Neurol. 2017;16:908–916. doi: 10.1016/S1474-4422(17)30328-9. - DOI - PMC - PubMed
1. Tan MMX, et al. Genome-wide association studies of cognitive and motor progression in Parkinson’s disease. Mov. Disord. 2021;36:424–433. doi: 10.1002/mds.28342. - DOI - PMC - PubMed
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Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

Collaborators

Affiliations

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

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