Objective: To assess the impact of genetically defined ancestry on progression of idiopathic Parkinson’s Disease and evaluate the contribution of known genetic variation on any identified effects.

Background: Parkinson’s Disease (PD) is a progressive, neurodegenerative disorder with a multifactorial aetiology. The interaction of environmental and genetic factors in its pathophysiology has been extensively studied with significant heterogeneity in progression of both its motor and non-motor symptoms noted across cohorts and ancestry groups. We aimed to assess the impact of genetically defined ancestry on progression to a composite outcome of death, dementia or clinical progression defined as Hoehn and Yahr stage 3 (HY3).

Method: Using data from 3 large cohorts of individuals with PD predominantly recruited in North America and Northern Europe comprising 3209 patients we used time-to-event analysis and the Cox Proportional Hazards Model to assess progression to our composite and individual outcomes in European (EUR), African (AFR), South Asian (SAS) and Ashkenazi Jewish (AJ) ancestry groups.

Results: A statistically significant difference in progression to the composite outcome across all ancestry groups was identified (p=0.002). Analyses of individual outcomes of death, dementia and HY3 showed that this effect is largely due to differences in progression to dementia when corrected for age, sex and cohort with individuals of AJ ancestry progressing more slowly (HR=0.17 (0.06-0.45); p=0.001) and individuals of AFR (HR = 6.46 (2.4 -17.4); p <0.001) and SAS (HR= 3.12 (1.29-7.56); p=0.012) ancestry progressing faster. We further analysed the effect of individuals with known genetic variants in LRRK2 and GBA1 on these effects – removal of individuals carrying pathogenic variants had only marginal effects on the hazard ratios.

Conclusion: Using a large cohort of individuals with a robust genetically defined ancestry we demonstrate differential progression to a composite unfavourable outcome with a specific signal for progression to dementia. We demonstrate that individuals of AFR and SAS ancestry progress faster in these domains and AJ slower compared to EUR individuals and that known genetic variation had no significant impact on these observed effects. These findings may relate to socio-economic, health care, co-morbidity or genetic factors and warrant further investigation.

References: 1. Ben-Joseph A, Marshall CR, Lees AJ, Noyce AJ. Ethnic Variation in the Manifestation of Parkinson’s Disease: A Narrative Review. Journal of Parkinson’s Disease. 2020;10(1):31.
2. Duarte Folle A, Flores MES, Kusters C, Paul KC, Del Rosario I, Zhang K, et al. Ethnicity and Parkinson’s Disease: Motor and Nonmotor Features and Disease Progression in Latino Patients Living in Rural California. J Gerontol A Biol Sci Med Sci. 2023 Jul 8;78(7):1258–68.
3. T X, C L, D L, H Y, M P, W K, et al. Disparities in diagnosis, treatment and survival between Black and White Parkinson patients. Parkinsonism & related disorders [Internet]. 2021 Jun [cited 2024 Jun 19];87. Available from: https://pubmed.ncbi.nlm.nih.gov/33905958/
4. Sauerbier A, Aris A, Lim EW, Bhattacharya K, Ray Chaudhuri K. Impact of ethnicity on the natural history of Parkinson disease. Medical Journal of Australia. 2018 May;208(9):410–4.
5. A S, A L, A A, Pk P. Nonmotor Symptoms in Parkinson’s Disease: Gender and Ethnic Differences. International review of neurobiology [Internet]. 2017 [cited 2024 Jun 19];133. Available from: https://pubmed.ncbi.nlm.nih.gov/28802927/
6. Branson CO, Ferree A, Hohler AD, Saint-Hilaire MH. Racial Disparities in Parkinson Disease: A Systematic Review of the Literature. Advances in Parkinson’s Disease. 2016 Nov 7;5(4):87–96.
7. Schumacher-Schuh AF, Bieger A, Okunoye O, Mok KY, Lim SY, Bardien S, et al. Underrepresented Populations in Parkinson’s Genetics Research: Current Landscape and Future Directions. Mov Disord. 2022 Aug;37(8):1593–604.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/impact-of-genetically-defined-ancestry-on-progression-of-idiopathic-parkinsons-disease/