Approved drugs, or drugs in development, target the protein products of 7 of the 234 genes (Supplementary Table 19a). This includes 3 high-priority genes CHRM3, SLC6A4 and CRHR1. CHRM3 and SLC6A4 were both implicated by novel signals (rs6688537:C>A in an intron of CHRM3 and rs59835752:-/A in an intron of EFCAB5, respectively) and encode targets for drugs approved for the treatment of asthma and COPD (CHRM3, muscarinic acetylcholine receptor M3) and anxiety and depression (SLC6A4, serotonin transporter). CRHR1 (implicated by rs35524223:T>A in an intron of KANSL1) encodes the corticotropin releasing factor receptor 1 which is a target for compounds in development for the treatment of anxiety, depression and irritable bowel syndrome. The other 4 genes include NDUFA12 (implicated by rs113745635:C>T in an intron of FGD6) encoding an NADH dehydrogenase which is a target for metformin hydrochloride, primarily used to treat type 2 diabetes, and ITK (implicated by rs10515750 in an intron of CYFIP2) encoding a tyrosine-protein kinase, a target for the cancer drug Pazopanib.
