The diverse smoking behaviors we investigated represent the spectrum of key events in an individual's smoking history from initiation (age at initiation, ever never smoking) thru establishment of dependency (smoking duration, smoking intensity, and pack years), to outcome (current versus former cigarette smoking status), with potential genetic influence at each stage. The finding that selected genes are associated with multiple phenotypes may represent both correlations among the phenotypes but also pleiotropic effects of the genes, and is a strength of the integrative approach [87]. Although we did not identify specific candidate regions that achieved the genomewide threshold of statistical significance, our study provides candidate genes for follow-up evaluation. Future GWAS studies with additional smoking behavioral measures, including nicotine dependence measures, the planned sharing of data across large consortia with increased sample size [88] and the functional analysis of individual SNPs [89], will be required to achieve the necessary power and specificity to understand SNP with low effects (OR<1.3), effects in subgroups, explore effect modification by demographic variables, and dissect pleiotropy.
