Towards a Global View of Parkinson's Disease Genetics

Abstract

Parkinson's disease (PD) is a global health challenge, yet historically studies of PD have taken place predominantly in European populations. Recent genetics research conducted in non-European populations has revealed novel population-specific genetic loci linked to PD risk, highlighting the importance of studying PD globally. These insights have broadened our understanding of PD etiology, which is crucial for developing disease-modifying interventions. This review comprehensively explores the global genetic landscape of PD, emphasizing the scientific rationale for studying underrepresented populations. It underscores challenges, such as genotype-phenotype heterogeneity and inclusion difficulties for non-European participants, emphasizing the ongoing need for diverse and inclusive research in PD. ANN NEUROL 2024;95:831-842.

Figure 1-. Schematic of genetic insights gained from genome-wide association studies across diverse populations.

The figure illustrates identified risk loci across five distinct ancestry populations: European, East Asian, South Asian, Latin American, and African/African admixed. Additionally, it highlights the novel identified loci through multi-ancestry analysis. Novel loci are shown in bold. “X pattern” denotes countries that participated in more than one population-specific GWAS. Orange color denotes East Asian ancestry origin including individuals from Singapore, Malaysia, Hong Kong, Taiwan, mainland China and Korea. Blue denotes African and African admixed ancestries and consists of individuals from the International Parkinson’s Disease Genomics Consortium-Africa, and participants from 23andMe. Green denotes Latin American ancestry consisting of LARGE PD participants from Uruguay, Peru, Chile, Brazil, Colombia, and Hispanic/Latino subjects from 23andMe. Purple denotes individuals recruited in India of South Asian ancestry.

Figure 2:. Schematic diagram of challenges in Parkinson's disease genetic research.