Genome‐wide interaction study of early‐life smoking exposure on time‐to‐asthma onset in childhood

Background Asthma, a heterogeneous disease with variable age of onset, results from the interplay between genetic and environmental factors. Early‐life tobacco smoke (ELTS) exposure is a major asthma risk factor. Only a few genetic loci have been reported to interact with ELTS exposure in asthma. Objective Our aim was to identify new loci interacting with ELTS exposure on time‐to‐asthma onset (TAO) in childhood. Methods We conducted genome‐wide interaction analyses of ELTS exposure on time‐to‐asthma onset in childhood in five European‐ancestry studies (totalling 8273 subjects) using Cox proportional‐hazard model. The results of all five genome‐wide analyses were meta‐analysed. Results The 13q21 locus showed genome‐wide significant interaction with ELTS exposure (P = 4.3 × 10−8 for rs7334050 within KLHL1 with consistent results across the five studies). Suggestive interactions (P