Genetic diversity shapes Parkinson’s disease risk across global populations
image: Flowchart detailing common genetic variants associated with PD risk based on GWAS data from European and non-European populations. (A) Genomic data can be collected from a new study of cohorts developed in European or multiethnic populations or from genetic information from biobanks or public repositories (such as GWAS catalog); (B) Data on top 10 common genetic variants associated with PD risk in the European population; (C) Data on genetic variants associated with PD risk identified in North American, Latin American, Korean, Amish, Ashkenazi Jewish, and Chinese populations. Underlined data represent variants associated with PD risk originally in a European population and replicated in other populations.
Credit: Júlio César Claudino dos Santos, Howard Lopes Ribeiro Junior, Jackson Frederico Pires, Gabriela Braga Cabrera Mano, Fabricyo de Faria Esposito Dias, João Vitor Caetano Goes, Camilla Teixeira Pinheiro Gusmão, André Rodrigues da Cunha Barreto-Vianna, Ettore José Filippi Carlo, Tayenne Nélly de Lucena Viana, Camila de Almeida Lins, Jonas Nogueira Ferreira Maciel Gusmão, Renata Ferreira de Carvalho Leitão.
Key Points:
Objective: The study aimed to review the role of common genetic variants in Parkinson’s disease (PD) risk among non-European populations, addressing the underrepresentation of these groups in genome-wide association studies (GWAS).
Background: PD is a neurodegenerative disorder with complex genetic and environmental influences. Most GWAS data come from European populations, limiting understanding of PD risk in other ethnicities.
Methods: A systematic review was conducted following PRISMA guidelines, analyzing GWAS studies from 2012 to 2023. The focus was on non-European populations, including North Americans, Latin Americans, Ashkenazi Jewish, Amish, Koreans, and Chinese.
Findings:
- SNCA, HLA, and MAPT were identified as key loci in North American and Latin American populations.
- MEGF10 was highlighted as a unique risk marker in the Amish population.
- GBA and LRRK2 variants were significant in Ashkenazi Jewish individuals.
- SNCA and LRRK2 were prominent in Korean patients.
- No consistent genetic pattern was found in Chinese populations, though SNCA, LRRK2, and novel loci (SV2C, WBSR17) showed associations.
Discrepancies: Variants identified in Europeans were not uniformly replicated in non-European groups, emphasizing the impact of ethnic diversity on genetic risk.
Implications: The study underscores the need for inclusive research to improve precision medicine for PD, ensuring treatments and risk assessments are effective across diverse populations.
Conclusion: The genetic architecture of PD varies by ethnicity, necessitating further studies to explore these differences and their clinical implications.
Significance: This review highlights the importance of diversifying genetic research to better understand PD risk and develop tailored therapies for global populations.