Previous research has related polymorphisms in the genes included in our genetic risk score to developmental phenotypes of smoking behavior24,26,32-35 and to mature phenotypes of adult smoking problems.29-31,56-58 To our knowledge, ours is the first study to track the relations of particular genetic risk variants with the development of smoking behavior from initiation through conversion to daily smoking and progression to heavy smoking, and on to the mature phenotypes of persistent of heavy smoking, nicotine dependence, and struggles with cessation through mid-life. Moreover, this extended follow-up allowed us to show, for the first time, that GWAS-identified variation in 15q25.1 and 19q13.2 influences adult smoking problems through a pathway mediated by adolescent progression from smoking initiation to heavy smoking. Our study is also the first to show that GWAS-identified SNPs provide information about smoking risks that cannot be ascertained from a family history, including information about risk for cessation failure.
