Category: Parkinson's Disease: Genetics
Objective: The aim of this study was to test for interactions between PD-related genetic and phenotypic traits in the 23andMe, Inc. research cohort.
Background: Parkinson’s disease (PD) is a neurodegenerative disorder that involves progressive neuronal loss and complex aetiology. Multiple genetic and environmental factors have been associated with PD, but most PD risk remains unexplained.
Method: Using a validated PD polygenic risk score (PRS) and common PD-associated variants in the GBA gene (N370S, E326K, T369M), we explored interactions between genetic susceptibility factors and seven phenotypic traits: body mass index (BMI), type 2 diabetes (T2D), tobacco use, caffeine consumption, pesticide exposure, head injury, and physical activity (PA).
Results: We observed that higher BMI, T2D, caffeine consumption, and tobacco use were associated with lower odds of PD, while head injury and pesticide exposure were associated with increased odds. No significant association between PA and PD was observed in the unstratified analysis. We observed that PRS was associated with increased odds of PD and statistical evidence for an interaction was observed between PRS and BMI, PRS and T2D, PRS and PA, and PRS and tobacco use (p=4.31e-4; p=6.50e-8; p=8.75e-5, p=2.24e-3 respectively). The inverse association between T2D and PD, BMI and PD, and tobacco use and PD was strongest in participants with lower genetic liability towards PD (lower PRS). A protective association between PA and PD was present in participants with lower PRS but not in those with a higher PRS, where PA was observed to be associated with higher disease risk. GBA carrier status was associated with PD, but there was no interaction with phenotypic traits.
Conclusion: Here we provide preliminary evidence that associations between phenotypic traits and PD may be modified by genotype. The findings warrant replication and further exploration to understand their potential relevance to intervention studies stratified by genotype.
To cite this abstract in AMA style:
R. Torricelli, A. Reynoso, B. Jacobs, J. Shi, S. Aslibekyan, L. Kaufmann, A. Noyce, K. Heilbron. Gene-environment interactions for Parkinson’s disease [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/gene-environment-interactions-for-parkinsons-disease/. Accessed May 9, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/gene-environment-interactions-for-parkinsons-disease/