p-values for ever vs never smoking (N=74,035 in the TAG consortium) ranged from 0.049 to 0.34 (Supplemental Table 9). We caution that the best DNTM3B signal in the TAG consortium was observed for CPD at only nominal significance (smallest P=0.027), despite having a nearly equivalent sample size as our study. However, our study yielding more statistically significant DNMT3B SNP associations with nicotine dependence (smallest P=3.7×10−8) is likely due to a combination of factors, including (1) reliance on FTND, a multi-dimensional phenotype that encompasses CPD and other important features of smoking behavior including TTFC that drove the rs910083 association, and (2) 1000G imputation which has been shown to strengthen association signals for some loci due to the finer mapping available.63, 64 We have similarly observed more statistically significant associations with nicotine dependence and stronger effect sizes, compared to CPD, in prior studies of CHRNB319 and CHRNA4.23
