in the follow‐up analysis. The signal on 11p13 no longer was significant at a genome‐wide level (P = 4.04e‐06); further, mediation analysis suggested that rs11031684 affects the hazard of progression to tolerance partly through smoking quantity. Interestingly, in the follow‐up analysis a novel genome‐wide significant signal emerged for rs2304808 on 9q34.12 within FUBP3, which belongs to a family of homologous gene‐regulatory proteins that regulate many common target genes. Mediation analysis further confirmed that the effect of rs2304808 was not mediated through smoking quantity. Inclusion of smoking quantity as a covariate substantially increased the significance of rs2304808, suggesting that including intermediate covariates may increase the power to detect SNPs that are independent of the covariates and directly associated with the phenotype.
