The Nigeria Parkinson Disease Registry: Process, Profile, and Prospects of a Collaborative Project

BACKGROUND: Clinical disease registries are useful for quality improvement in care, benchmarking standards, and facilitating research. Collaborative networks established thence can enhance national and international studies by generating more robust samples and credible data and promote knowledge sharing and capacity building. This report describes the methodology, baseline data, and prospects of the Nigeria Parkinson Disease Registry. METHODS: This national registry was established in November 2016. Ethics approval was obtained for all sites. Basic anonymized data for consecutive cases fulfilling the United Kingdom Parkinson's Disease Brain Bank criteria (except the exclusion criterion of affected family members) are registered by participating neurologists via a secure registry website (www.parkinsonnigeria.com) using a minimal common data capture format. RESULTS: The registry had captured 578 participants from 5 of 6 geopolitical zones in Nigeria by July 2019 (72.5% men). Mean age at onset was 60.3 ± 10.7 years; median disease duration (interquartile range) was 36 months (18–60.5 months). Young‐onset disease (<50 years) represented 15.2%. A family history was documented in 4.5% and 7.8% with age at onset <50 and ≥ 50, respectively. The most frequent initial symptom was tremor (45.3%). At inclusion, 93.4% were on treatment (54.5% on levodopa monotherapy). Per‐capita direct cost for the registry was $3.37. CONCLUSIONS: This is the first published national Parkinson's disease registry in sub‐Saharan Africa. The registry will serve as a platform for development of multipronged evidence‐based policies and initiatives to improve quality of care of Parkinson's disease and research engagement in Nigeria

Identification of genetic risk loci and causal insights associated with Parkinson\u27s disease in African and African admixed populations: a genome-wide association study

\ua9 2023 Elsevier LtdBackground: An understanding of the genetic mechanisms underlying diseases in ancestrally diverse populations is an important step towards development of targeted treatments. Research in African and African admixed populations can enable mapping of complex traits, because of their genetic diversity, extensive population substructure, and distinct linkage disequilibrium patterns. We aimed to do a comprehensive genome-wide assessment in African and African admixed individuals to better understand the genetic architecture of Parkinson\u27s disease in these underserved populations. Methods: We performed a genome-wide association study (GWAS) in people of African and African admixed ancestry with and without Parkinson\u27s disease. Individuals were included from several cohorts that were available as a part of the Global Parkinson\u27s Genetics Program, the International Parkinson\u27s Disease Genomics Consortium Africa, and 23andMe. A diagnosis of Parkinson\u27s disease was confirmed clinically by a movement disorder specialist for every individual in each cohort, except for 23andMe, in which it was self-reported based on clinical diagnosis. We characterised ancestry-specific risk, differential haplotype structure and admixture, coding and structural genetic variation, and enzymatic activity. Findings: We included 197 918 individuals (1488 cases and 196 430 controls) in our genome-wide analysis. We identified a novel common risk factor for Parkinson\u27s disease (overall meta-analysis odds ratio for risk of Parkinson\u27s disease 1\ub758 [95% CI 1\ub737–1\ub780], p=2\ub7397 7 10−14) and age at onset at the GBA1 locus, rs3115534-G (age at onset β=–2\ub700 [SE=0\ub757], p=0\ub70005, for African ancestry; and β=–4\ub715 [0\ub758], p=0\ub7015, for African admixed ancestry), which was rare in non-African or non-African admixed populations. Downstream short-read and long-read whole-genome sequencing analyses did not reveal any coding or structural variant underlying the GWAS signal. The identified signal seems to be associated with decreased glucocerebrosidase activity. Interpretation: Our study identified a novel genetic risk factor in GBA1 in people of African ancestry, which has not been seen in European populations, and it could be a major mechanistic basis of Parkinson\u27s disease in African populations. This population-specific variant exerts substantial risk on Parkinson\u27s disease as compared with common variation identified through GWAS and it was found to be present in 39% of the cases assessed in this study. This finding highlights the importance of understanding ancestry-specific genetic risk in complex diseases, a particularly crucial point as the Parkinson\u27s disease field moves towards targeted treatments in clinical trials. The distinctive genetics of African populations highlights the need for equitable inclusion of ancestrally diverse groups in future trials, which will be a valuable step towards gaining insights into novel genetic determinants underlying the causes of Parkinson\u27s disease. This finding opens new avenues towards RNA-based and other therapeutic strategies aimed at reducing lifetime risk of Parkinson\u27s disease. Funding: The Global Parkinson\u27s Genetics Program, which is funded by the Aligning Science Across Parkinson\u27s initiative, and The Michael J Fox Foundation for Parkinson\u27s Research