Currently, developing new therapeutics for TUD is viewed as risky because of a lack of high-quality targets, historically low success rates, and unintended side effects. Although genes identified in our GWAS, including CHRNA5, CHRNA4, and CHRNB2, might moderate the effect of varenicline, a smoking cessation treatment that operates as a partial agonist at the nicotine acetylcholine a2b4 receptor,60 varenicline (along with other medications such as nicotine replacement therapies) has limited efficacy or adverse effects.61,62 In a proof-of-principle study, So et al.63 identified several repurposing candidates for treating psychiatric disorders by connecting imputed transcriptomic profiles from GWAS data to drug-induced gene expression profiles. Using this approach, we identified hundreds of potential drug candidates predicted to significantly reverse the TUD transcriptomic profile. These included norepinephrine reuptake inhibitors (e.g., amoxapine) and antipsychotics (e.g., clozapine), pointing to convergent molecular mechanisms between TUD and other psychiatric disorders that are the usual target of these agents, replicating prior observations.64,65 The potential therapeutic utility of anti-inflammatory and blood glucose lowering medications was also suggested by our analyses, in addition to an anti-Parkinson medication known to interact with
