A second signal of association with FEV1 extremes on chromosome 17 (17q25.1) was within TSEN54 and occurred only in never smokers (rs7218675; p=1·18 × 10−8; table 2). TSEN54 encodes a subunit of the tRNA splicing endonuclease complex, and rs7218675 was associated with expression of KIAA0195, TSEN54, and GRB2 in blood and expression of GRB2 in lung tissue (appendix pp 63–66). GRB2 is a ligand of the epidermal growth factor receptor, which links signalling by epidermal growth factor with the MAPK/ERK signalling pathway, triggering cell proliferation. RNA sequencing in human bronchial epithelial cells identified a relatively abundant novel fusion transcript of TSEN54 and LLGL2 (appendix p 108).
