Linking transcriptome-wide patterns to perturbagens that pass the blood-brain barrier from the Library of Integrated Network-Based Cellular Signatures (LINCS)36 database identified 235 medications approved by the U. S. Food and Drug Administration (Supplementary Table 30). Of the 235 identified medications, 20 targeted at least one mapped/independent gene from our GWAS (Figure 4). The medications that significantly reversed (Bonferroni p<6.03E-05) the transcriptional profile associated with TUD included varenicline (a well-known therapeutic for smoking cessation), sodium channel blockers (e.g., amiloride), and compounds that are used to treat conditions that commonly co-occur with TUD, such as antipsychotics (e.g., clozapine), dopaminergic agents (e.g., ropinirole), opioids (e.g., nalbuphine), and antidepressants (e.g., amoxapine), among others (Supplementary Table 30).
