Advancing Parkinson's Disease Research in Africa: A Strategic Training Framework of the Global Parkinson's Genetics Program

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder with diverse motor, nonmotor, and neuropsychiatric symptoms. Genetic and environmental factors contribute to its development.¹ However, PD research has predominantly focused on individuals of European descent, with over 80% of genome-wide association studies (GWAS) centered on this group.² This lack of diversity limits our understanding of disease mechanisms and creates disparities, preventing the equitable implementation of personalized medicine.^2-4 Collaborative efforts are underway to enhance diversity in PD genetic research.

Africa is the second most populous continent and is expected to host 26% of the global population by 2050.⁵ Despite exhibiting the highest genetic variation and complex admixture, African populations are significantly underrepresented in PD research, with only a fraction of their extensive genetic diversity being surveyed,⁶ primarily focusing on Mendelian genes associated with monogenic PD.^{2, 7, 8} Genetic studies have characterized a limited number of Africa's 2000 ethnolinguistic groups, mainly using genotyping arrays with variants common in Europeans, leaving the distribution of novel, rare, and medically relevant variations largely unknown.⁸ For instance, although the LRRK2 p.G2019S variant is present in 1% to 2% of Europeans PD patients,⁹ 29.7% of familial Ashkenazi Jewish PD patients,¹⁰ and 40% of North African Arabs,¹¹ it has not been identified in Black Africans to date.¹² Given Africa's ethnic and genetic diversity, including these populations is crucial for understanding novel genetic determinants underlying PD risk, onset, and progression.¹³

Research capacity and research infrastructure in Africa remain limited, with PD genetic research facing challenges, including political and economic instability, a predominant focus on infectious diseases, limited medical personnel, and insufficient funds and infrastructure.¹²

A recent global effort, the Global Parkinson's Genetics Program (GP2, www.gp2.org), supported by Aligning Science Across Parkinson's (ASAP), aims to address the need for diversity in PD research. GP2 is expanding to include at-risk populations and patients with “atypical” parkinsonism. The principal aims of GP2 extend beyond enhancing our understanding of the genetic factors in PD across global populations; it also seeks to transform this knowledge into practical applications. Achieving this vision entails creating a unified network of collaborators; conducting large-scale data collection, analysis, and harmonization; and training analysts worldwide. To achieve this, GP2 allocates funds and resources to support PD genetic research and capacity building in underrepresented regions, with a focus on retaining local scientists to ensure a lasting impact.³²

In collaboration with GP2, the Transforming Parkinson's Case in Africa (TRaPCAf-GP2) study is underway across seven African countries and is expected to contribute 1000 PD patients and 2000 controls to GP2.⁴⁰ Furthermore, IPDGC Africa plans to expand its recruitment to 12 French-speaking countries to enhance GP2's coverage across Africa. GP2 is committed to performing WGS on all African PD patients to aid in identifying novel PD variants. As of June 2024, GP2 has 55 active projects, 22 involving African trainees and collaborators, emphasizing the contribution from both early-career and established researchers. The TN-WG is actively developing new training resources for African PD researchers, including in-person bioinformatics workshops, with one scheduled for Morocco in November 2024.

Upon completion of GP2, we anticipate a significant increase in professionals skilled in clinical research, genetics, and bioinformatics, along with strengthened collaborations among these experts, which will drive substantial progress in PD research in Africa. Ultimately, building strong partnerships with African institutions and encouraging their active involvement are crucial for the long-term sustainability of the initiative.

(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique

K.S.: 1A, 1B, 1C, 3A

E.E.: 3A

I.E.: 3A

N.R.: 3A

N.O.: 3B

R.W.: 3B

W.M.: 3B

M.R.: 3B

S.B.-C.: 3B

A.J.N.: 3B

S.D.: 3B

S.B.: 1A, 3B

M.T.P.: 1A, 3A, 3B

K.S. is funded by the Michael J. Fox Foundation (MJFF) and Aligning Sciences Across Parkinson's Disease Global Parkinson Genetic Program (ASAP-GP2). N.O. has the following financial disclosures: MJFF and Tertiary Education Trust Fund (TETFUND) National Research Fund. R.W. is supported by the Transforming Parkinson's Care in Africa (TraPCAf), MJFF, Aligning Science Across Parkinson's (ASAP), the genetic profile of Parkinson's Disease in Africa). I.E. received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 945425 (‘DevelopMed’). A.J.N. reports grants from Parkinson's UK, Barts Charity, Cure Parkinson's, NIHR, Innovate UK, Virginia Keiley benefaction, Alchemab, ASAP, and MJFF. Consultancy and personal fees from Astra Zeneca, AbbVie, Profile, Roche, Biogen, UCB, Bial, Charco Neurotech, uMedeor and Britannia. S.D. is funded by the MJFF. S.B. is supported in part by the South African Medical Research Council [Self-Initiated Research Grant]; the National Research Foundation of South Africa [Grant number 129249]; and the South African Medical Research Council/Stellenbosch University Genomics of Brain Disorders Research Unit, Cape Town, South Africa. E.E., M.R., W.M., N.R., S.B.-C, and M.T.P. have nothing to disclose.