The 68 genes identified as high-priority included genes at novel signals encoding targets for which there are approved drugs or drugs in development (Supplementary Table 19). Of note, the muscarinic acetylcholine receptor M3, encoded by CHRM3, is a well-characterised drug target for which many approved drugs exist, including for the treatment of asthma and obstructive lung disease. SLC6A4 encodes a serotonin transporter, a target for a number of drugs approved for treating depression and anxiety disorders, one of which (nortriptyline hydrochloride) has been trialed for use in inflammatory skin disorders (psoriasis and eczema); HTR4, which encodes a serotonin receptor, was identified in one of the earliest lung function GWAS13. INPP5E, identified as a high-priority gene for a novel signal of association with FVC (and FEV1) on chromosome 9, encodes inositol polyphosphate-5-phosphatase E, a component of the inositol phosphate metabolism pathway. Another component of the same pathway, phosphoinositide 3-kinase (PI3K) delta is a target of drugs under development for the treatment of a range of indications including COPD and asthma. Mutations in INPP5E cause ciliopathy (Joubert and MORM syndromes).
