Genetic Considerations in Deep Brain Stimulation for Parkinson's Disease
Summary
Parkinson’s disease is clinically heterogeneous, with approximately 5–10% of cases linked to monogenic mutations. Deep brain stimulation (DBS) of the subthalamic nucleus and globus pallidus internus is a mainstay for advanced motor symptoms, yet genetic differences influence both efficacy and long-term outcomes. Variants in LRRK2, GBA1 and PRKN represent the most common monogenic contributors. LRRK2 mutation carriers typically demonstrate marked motor improvement and sustained reduction in dopaminergic medication, whereas GBA1 mutation carriers may experience accelerated cognitive decline and poorer non-motor outcomes following DBS. PRKN mutation carriers often present at a younger age with pronounced motor benefit and minimal cognitive side effects. Genetic stratification is increasingly used to guide patient selection, refine target localisation and tailor stimulation parameters. Recent mechanistic studies have elucidated the role of mitochondrial quality control and lysosomal function in mediating DBS-induced neuroprotection, suggesting genotype-dependent variations in neurophysiological response. The integration of genetic testing into routine clinical workflows is poised to enhance personalised therapy and improve prognostic accuracy. Globally, harmonised protocols for genetic screening and phenotype characterisation within DBS programmes are essential to enable equitable access to precision neuromodulation in Parkinson’s disease.
Research from Nature Portfolio
No recent Nature Portfolio content available.
Genetic Considerations in Deep Brain Stimulation for Parkinson's Disease publication trend
The graph below shows the total number of articles in genetic considerations in deep brain stimulation for parkinson's disease across all publications each year (not limited to Nature Index journals).
Technical terms
Deep brain stimulation (DBS): A neurosurgical procedure that delivers electrical impulses to specific brain regions to modulate neural circuits and ameliorate motor symptoms in Parkinson’s disease.
Monogenic Parkinson’s disease: A subset of Parkinson’s disease caused by a single-gene mutation, often with distinct clinical trajectories compared with idiopathic cases.
LRRK2: Leucine-rich repeat kinase 2 gene, mutations of which are the most common cause of autosomal dominant familial Parkinson’s disease.
GBA1: Glucocerebrosidase gene, variants of which increase Parkinson’s disease risk and are associated with more rapid progression of motor and cognitive symptoms.
Parkin (PRKN): Gene encoding an E3 ubiquitin ligase, mutations of which lead to early-onset Parkinson’s disease with generally favourable DBS outcomes.
Phenotypic heterogeneity: Variation in symptom presentation, disease progression and treatment response among individuals with Parkinson’s disease, influenced by genetic and environmental factors.
References
- Subthalamic nucleus deep brain stimulation alleviates oxidative stress via mitophagy in Parkinson’s disease. npj Parkinson's Disease (2024).
- Association of Subthalamic Deep Brain Stimulation With Motor, Functional, and Pharmacologic Outcomes in Patients With Monogenic Parkinson Disease. JAMA Network Open (2019).
- Deep brain stimulation for monogenic Parkinson’s disease: a systematic review. Journal of Neurology (2019).
- Genotype and phenotype in Parkinson's disease: Lessons in heterogeneity from deep brain stimulation. Movement Disorders (2013).
- Greater improvement in LRRK2 G2019S patients undergoing Subthalamic Nucleus Deep Brain Stimulation compared to non-mutation carriers. BMC Neuroscience (2016).
- Deep brain stimulation and genetic variability in Parkinson’s disease: a review of the literature. npj Parkinson's Disease (2019).
- Should we offer deep brain stimulation to Parkinson’s disease patients with GBA mutations?. Frontiers in Neurology (2023).
- The Role of Genetic Data in Selecting Device-Aided Therapies in Patients With Advanced Parkinson’s Disease: A Mini-Review. Frontiers in Aging Neuroscience (2022).
- Precision Medicine in Parkinson’s Disease: From Genetic Risk Signals to Personalized Therapy. Brain Sciences (2022).
About these summaries
This Nature Research Intelligence Topic summary is created with the cited references and a large language model. We take care to ground generated text with facts, and have systems in place to gain human feedback on the overall quality of the process in line with our AI principles. We strive to create accurate and useful summaries for people unfamiliar with the research topic and that supports this goal. These pages are a beta release and will be updated as we learn how best to help people gain value from a research topic summary.
Turn complex research questions into confident strategic decisions
When you're under pressure to set direction, justify investment, or understand your competitive position, you need more than raw data — you need trusted insights you can act on.
Benchmark your performance against global peers using robust, methodologically sound analysis.
Combine quantitative metrics with qualitative expert insight to uncover strengths, gaps and emerging opportunities.
Gain tailored, decision-ready recommendations aligned to your strategic priorities.
Talk to us to learn more about our data dashboards and bespoke strategy reports.
Grow research skills, confidence and careers with training built for every stage of the research lifecycle.
Developed with Nature Portfolio journal Editors and internationally renowned experts. Discover three ways to learn:
Self-paced, online courses in convenient bite-sized units, covering key skills across scientific writing, publishing, grant writing, data analysis, and more.
Expert trainer-led workshops with hands-on exercises and real-time feedback across core research skills, delivered via interactive group sessions.
Editor-led workshops combining core principles in writing and publishing, personalised 1:1 feedback from Nature Portfolio Editors and hands-on exercises.
Explore course catalogues and workshop agendas, enquire about the options or request institutional pricing.