Identification of Exercise-Related Signature Genes Potentially Associated with Cocaine Addiction by Integrating
Jinke He1,2, Xiaoyu Deng1,3, Yuxuan Deng1,4
1Hunan Provincial Key Laboratory of Dong Medicine, Biomedical Research Institute, Hunan University of Medicine, Huaihua 418000, China.
Genes
|December 30, 2025
Summary
Exercise may protect against cocaine addiction by influencing specific genes related to immune responses and metabolism. Mendelian randomization analysis suggests a causal link, identifying six key genes as potential therapeutic targets for addiction treatment.
Area of Science:
- Neuroscience and Genetics
- Addiction Research
- Molecular Biology
Background:
- Exercise is a potential non-pharmacological treatment for cocaine addiction.
- The molecular mechanisms linking exercise and cocaine addiction are not well understood.
- Identifying exercise-related genes in cocaine addiction is crucial for developing targeted therapies.
Purpose of the Study:
- To identify exercise-related signature genes associated with cocaine addiction.
- To investigate the potential causal relationship between exercise and cocaine addiction using Mendelian randomization (MR).
Main Methods:
- Analysis of midbrain transcriptomic data to identify differentially expressed genes (DEGs) and exercise-related genes.
- Functional enrichment, protein-protein interaction (PPI), and immune infiltration analyses.
- Screening and validation of signature genes using LASSO, Random Forest, ROC curves, and Gene Set Enrichment Analysis (GSEA).
- Two-sample Mendelian randomization (MR) analysis to assess causality.
Main Results:
- Six signature genes (CALM3, CCL2, CD44, CLIC1, JUN, VCAM1) were identified with high diagnostic accuracy (AUC 0.714–0.868).
- Functional analyses indicated enrichment in immune-inflammatory pathways, metabolic processes, and neuro-immune interactions.
- Cocaine addiction was associated with altered immune cell profiles and immune dysregulation linked to signature genes.
- MR analysis revealed a significant protective association between genetically predicted higher exercise levels and reduced cocaine addiction risk.
Conclusions:
- The six identified genes may serve as potential biomarkers and therapeutic targets for cocaine addiction.
- Exercise may exert protective effects against cocaine addiction through modulation of immune-inflammatory responses, metabolic pathways, and neuroplasticity.
- Further validation in larger cohorts and experimental models is warranted.
Keywords:
Mendelian randomizationbioinformaticscocaine addictionexerciseimmune infiltrationsignature genes
