Objective: The objective of this study was to evaluate the effect of SNPs in BDNF on depressive symptomatology in a sample of individuals with PD.

Background: Parkinson’s disease (PD) is a neurodegenerative disease characterized by motor and non-motor symptoms. Depression is a common non-motor symptom in PD that impacts the quality of life of patients and their caregivers. Single-nucleotide polymorphisms (SNPs) have been associated with PD and depressive phenotypes, such as in the brain-derived neurotrophic factor (BDNF) gene, which promotes neuroprotection and neuroregeneration.

Method: Whole-genome sequencing data and Beck Depression Inventory (BDI) scores from European individuals with PD were obtained from the Global Parkinson’s Genetic Program Release 11. Depressive symptomatology was defined as BDI score ≥14. Burden tests using Sequence Kernel Association Test (SKAT) and Optimal Sequence Kernel Association Test (SKAT-O) were conducted for coding variants with RVTests. Association analyses were performed both unadjusted and adjusted for age, sex, and the first five principal components for all variants and coding variants in BDNF using PLINK 2.0. Finally, nominally significant variants were annotated using Variant Effect Predictor from Ensembl and Franklin database.

Results: The analysis included 50 individuals with depressive symptomatology and 346 controls. Burden tests of coding and all BDNF variants showed no nominal association with depressive symptomatology. Association analyses using the unadjusted model identified 42 variants, and the adjusted model identified 18 variants with nominal significance. The annotated variants identified in both models were intronic or non-coding and classified as benign, except for rs191686551 found in the adjusted model, which was annotated as having uncertain pathogenicity in the Franklin database.

Conclusion: The identified variants of BDNF annotated as benign in intronic regions may not have a direct functional role, and further analyses are needed to elucidate the association between PD and BDNF reported in earlier literature. Future analyses will replicate these methods in another European cohort using the Geriatric Depression Scale and in a Latin American cohort using the State-Trait Depression Inventory.

References: WHO. (2023). Parkinson’s Disease. https://www.who.int/es/news-room/fact-sheets/detail/parkinson-disease
The Global Parkinson’s Disease Survey (GPDS) Steering Committee. Factors impacting on quality of life in Parkinson’s disease: Results from an international survey. (2002). Movement Disorders, 17(1), 60–67.
Palasz, E., et al. (2020). BDNF as a Promising Therapeutic Agent in Parkinson’s Disease. International journal of molecular sciences, 21(3), 1170.
Cagni, F. C., et al. (2016). Association of BDNF Val66MET Polymorphism With Parkinson’s Disease and Depression and Anxiety Symptoms. Journal of Neuropsychiatry, 29(2), 142–147.
Global Parkinson’s Genetic Program (2025) GP2 Release 11. DOI 10.5281
Purcell, S., et al. (2007). PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses. The American Journal of Human Genetics, 81(3), 559–575.
Dyer, S. C., et al. (2024). Ensembl 2025. Nucleic Acids Research, 53(D1), D948–D957. https://doi.org/10.1093/nar/gkae1071
https://franklin.genoox.com—Franklin by Genoox
Xiaowei Zhan, et al. RVTESTS: An Efficient and Comprehensive Tool for Rare Variant Association Analysis Using Sequence Data. Bioinformatics 2016 32: 1423-1426‌

« Back to 2026 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/analysis-of-genetic-variants-associated-with-parkinsons-disease-and-depression/