We have extended the original TAG analysis and the previous work that has implicated SNPs and genes in smoking behaviours. Our results illustrate the utility of secondary analyses of published, publicly-available datasets, and demonstrate that following-up the SNP-based tests by gene- and pathway analyses can lead to considerable gains in statistical power and can yield important insights into the biological mechanisms underlying the trait of interest. The gene-based analysis revealed twenty-one genes implicated in smoking behaviours. Of these, fifteen are novel and were missed with the SNP-based approach in the original TAG analysis. Aside from the known cluster of genes (IREB2-CHRNA3-CHRNA5-CHRNB4-HYKK-PSMA4), we identified a cluster of three loci on the same chromosome 15 (ADAMTS7, MORF4L1 and LOC646938, P=4.48E-17, 1.18E-06 and 1.66E-05, respectively). The ADAMTS7-MORF4L1 locus has been previously associated with e.g., coronary artery disease 30 for which smoking is a known risk factor. Based on a joint-analysis, SNPs within ADAMTS7 and MORF4L1 were recently listed as candidate signals for smoking behaviour independent of those yielded by the known loci rs16969968 or rs588765 in CHRNA5 31. Regarding the two significant associations
