Work

Mendelian Randomization Uncovers Potential Repurposable Medications for Neuropsychiatric Disorders

Year: 2025

Type: article

Abstract: BACKGROUND: The growing prevalence of neuropsychiatric disorders is becoming a major health challenge. Traditional pharmacotherapies face limitations, making drug repurposing a valuable strategy. However, high-throughput screening approaches for these conditions are scarce. METHODS: This study leveraged exposure data from the UK Biobank Neale Lab (N = 361,141) and outcome data from the FinnGen database (N = approximately 410,000) to employ Mendelian Randomization (MR) analyses and identify potential drug repurposing candidates for neuropsychiatric disorders. Sensitivity, Linkage Disequilibrium Score Correlation (LDSC), and Bayesian Colocalization (COLOC) analyses were conducted to ensure the robustness and reliability of our findings. RESULTS: Using the IVW method, seven medications with negative causal associations with neuropsychiatric disorders were identified. Pregabalin, bumetanide, and prednisolone were associated with reduced anxiety (beta = -7.28, p = 4.00e-03; beta = -2.24, p = 6.00e-03; beta = -1.74, p = 2.84e-03). Vitamin B1 preparations showed an inverse association with dementia (beta = -2.47, p = 1.51e-03), Creon E/C granules with epilepsy (beta = -4.99, p = 3.91e-03), Pentasa SR 250 mg with multiple sclerosis (beta = -3.95, p = 3.83e-03), and zolmitriptan with stroke excluding subarachnoid hemorrhage (beta = -1.61, p = 6.00e-03). Sensitivity analyses confirmed these findings, whereas the LDSC and COLOC analyses provided additional support. CONCLUSION: MR-based drug repurposing is a promising approach for the treatment of neuropsychiatric disorders. Further validation is necessary to effectively integrate these medications into clinical practice.

Source: Current Neuropharmacology

DOI: 10.2174/011570159x368382250527073353

Authors: Xiao Xiao, Tingyu Li, Qiang Wang, Linbo Gao, Shanling Liu, Lin Zhang

Institutions: Sichuan University, West China Second University Hospital of Sichuan University

Language: English

Topic: Genetic Associations and Epidemiology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities