A potential drug target in epilepsy and its role in other neurological disorders

Epilepsy (EP) has an increased incidence due to several diseases, including neurodegenerative diseases and hemorrhagic stroke. The proteome-based research on developing suitable therapeutic interventions and disease prevention is beneficial. Cis-acting protein quantitative trait loci from 885 plasma and CSF proteins were used to explore potential drug targets for EP. After we got the preliminary association of TMEM106B with EP by drug target Mendelian randomization (MR), co-localization results identified TMEM106B as a potential drug target for EP further. The protein-protein interaction network indicated the interaction of proteins. Drug target MR and two-sample MR showed the role of TMEM106B in other 7 neurological diseases such as Alzheimer's disease (AD) and intracerebral hemorrhage (ICH). We included sensitivity tests, reverse MR, Steiger filtering, and phenotype scanning to strengthen our conclusion. We identified TMEM106B as a potential drug target for EP (P = 1.29 × 10^-5; co-localization-PPH₄ = 0.796) and AD (P = 6.11 × 10^-7; co-localization-PPH₄ = 0.947). Fifty-eight plasma and 13 CSF proteins have suggestive causal relationships with EP (P < 0.05), and both GRN and APOE interact with TMEM106B. TMEM106B has a causal relationship with ICH (P = 5.00 × 10^-3). AD has a causal relationship with TMEM106B (P = 3.79 × 10^-3). TMEM106B in plasma is a protection factor for EP and a risk factor for AD and ICH. AD might induce a lower level of TMEM106B in plasma. TMEM106B which is associated with GRN and APOE might be a promising drug target for both EP and AD.