Comprehensive genetic screening of the South African Parkinson's disease study collection using the NeuroBooster array.
13 affiliations
- 1South African Medical Research Council Centre for Tuberculosis Research (CTR); Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
- 2Biomedical Research Institute (BMRI), Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
- 3Center 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.
- 4DataTecnica LLC, Washington, DC 20037, USA.
- 5Division of Immunology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
- 6School for Data Science and Computational Thinking, Stellenbosch University, Cape Town, South Africa.
- 7Center for Bioinformatics and Computational Biology, Stellenbosch University, Cape Town, South Africa.
- 8Division of Neurology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
- 9South African Medical Research Council/Stellenbosch University Genomics of Brain Disorders Research Unit, Stellenbosch University, Cape Town, South Africa.
- 10Department of Neurology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
- 11National Institute for Theoretical and Computational Sciences (NITheCS), Stellenbosch, South Africa.
- 12Genomics for Health in Africa (GHA), Africa-Europe Cluster of Research Excellence (CoRE), South Africa.
- 13Genome Sciences and Systems Biology, Cleveland Clinic Research, Cleveland Clinic Foundation, Cleveland, United States.
Abstract
Introduction
Although there have been significant advances in the genetic etiology of Parkinson's disease (PD), most of this research has been conducted in European populations. This study aimed to characterize the genetic landscape of PD in South Africa, whose populations are renowned for their extensive genetic diversity and admixture.Methods
We recruited 689 PD probands across South Africa. These participants were genotyped using the NeuroBooster array in collaboration with the Global Parkinson's Genetics Program (GP2). An in-house computational workflow was used to identify pathogenic missense variants, which were validated using Sanger sequencing. The CNV-Finder pipeline was used to screen for copy number variations (CNVs), which were validated using Multiplex Ligation-dependent Probe Amplification (MLPA). Previously identified pathogenic variants were used as positive controls in our analysis.Results
We identified 16 unique missense variants in 47 individuals, 15 of which were independently confirmed by Sanger sequencing. However, these variants are not considered likely to be associated with PD status. We also identified new homozygous PRKN CNVs in three individuals and a whole-gene SNCA duplication in one individual, all of which were validated by MLPA. In addition, one individual had a CNV in the 5' untranslated region of SNCA, although its pathogenicity remains unclear. When these findings were combined with our previous results, 3.5% of probands (24 individuals) were found to have a genetic basis for their disease.Conclusions
We conducted the largest pathogenic variant screening to date in this unique and underrepresented population, and our findings highlight the rare contribution of known pathogenic variants. This study underscores the importance of expanding genetic research in African cohorts to improve global understanding of PD etiology.
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BibTeX
@article{step2026comprehensive,
title = {{Comprehensive genetic screening of the South African Parkinson's disease study collection using the NeuroBooster array.}},
author = {Kathryn Step and Lusanda Madula and Nicole Kuznetsov and Elizna Maasdorp and Jonathan Carr and Riaan van Coller and Marlo Möller and Ignacio F Mata and Soraya Bardien and Global Parkinson's Genetics Program (GP2)},
journal = {Clinical parkinsonism \& related disorders},
year = {2026},
month = oct,
doi = {10.1016/j.prdoa.2026.100508},
url = {https://europepmc.org/article/MED/42890374},
note = {CC BY},
}
RIS
TY - JOUR
TI - Comprehensive genetic screening of the South African Parkinson's disease study collection using the NeuroBooster array.
AU - Kathryn Step
AU - Lusanda Madula
AU - Nicole Kuznetsov
AU - Elizna Maasdorp
AU - Jonathan Carr
AU - Riaan van Coller
AU - Marlo Möller
AU - Ignacio F Mata
AU - Soraya Bardien
AU - Global Parkinson's Genetics Program (GP2)
PY - 2026
DA - 2026/10/02
JO - Clinical parkinsonism & related disorders
DO - 10.1016/j.prdoa.2026.100508
UR - https://europepmc.org/article/MED/42890374
AB - Introduction Although there have been significant advances in the genetic etiology of Parkinson's disease (PD), most of this research has been conducted in European populations. This study aimed to characterize the genetic landscape of PD in South Africa, whose populations are renowned for their extensive genetic diversity and admixture.Methods We recruited 689 PD probands across South Africa. These participants were genotyped using the NeuroBooster array in collaboration with the Global Parkinson's Genetics Program (GP2). An in-house computational workflow was used to identify pathogenic missense variants, which were validated using Sanger sequencing. The CNV-Finder pipeline was used to screen for copy number variations (CNVs), which were validated using Multiplex Ligation-dependent Probe Amplification (MLPA). Previously identified pathogenic variants were used as positive controls in our analysis.Results We identified 16 unique missense variants in 47 individuals, 15 of which were independently confirmed by Sanger sequencing. However, these variants are not considered likely to be associated with PD status. We also identified new homozygous PRKN CNVs in three individuals and a whole-gene SNCA duplication in one individual, all of which were validated by MLPA. In addition, one individual had a CNV in the 5' untranslated region of SNCA, although its pathogenicity remains unclear. When these findings were combined with our previous results, 3.5% of probands (24 individuals) were found to have a genetic basis for their disease.Conclusions We conducted the largest pathogenic variant screening to date in this unique and underrepresented population, and our findings highlight the rare contribution of known pathogenic variants. This study underscores the importance of expanding genetic research in African cohorts to improve global understanding of PD etiology.
SN - 2590-1125
ER -