In the analysis of smoking cessation we found that being a female, scoring higher in ND, and stronger nicotine withdrawal symptoms predicts slower transition to quitting, whereas later age of daily smoking predicts faster quitting. In the time‐to‐event analysis we detected genome‐wide significant association with rs72779075 on 10p14, located 35 kb from a pseudogene RP11‐575N15 and around 725 kb downstream of GATA3. In the follow‐up analysis the signal of this SNP was no longer significant; however, our mediation analysis showed no statistically significant evidence for the effect of rs72779075 being mediated by ND or nicotine withdrawal symptoms, and thus the effect on difficulty in achieving and maintaining abstinence is likely due to other mechanisms besides the severity of ND and withdrawal. Interestingly, nicotine upregulates expression of GATA3 through stimulation of nAChRs (Arredondo et al. 2006). GATA3 is crucial in inducing allergic airway inflammation (Barnes 2008); although rs72779075 is located 725 kb downstream of GATA3, it may tag variants that influence symptoms of airway inflammation and thus may motivate smokers to quit. Alternatively, RP11‐575N15 may have an unidentified function. Transcripts produced from pseudogenes may, for example, regulate the effects of microRNAs on their targets by competing for microRNA binding (Swami 2010).
