In this paper, we examine genotype-phenotype associations with nicotine dependence, and investigate whether modeling statistical interactions between SNP and age-at-onset of regular smoking (AOS) can increase the amount of variation explained by genetic polymorphisms. Specifically, we posit that early and late onset smokers are likely to differ in terms of etiology for development of nicotine dependence, and that this will result in differences in the relative influence of polymorphisms as a function of AOS. We take a large-scale candidate gene approach (i.e., 3,369 SNPs from 348 genes) using data from the Collaborative Study for the Genetics of Nicotine Dependence (COGEND), a case-control study of the genetics of nicotine dependence among smokers. Because we are interested in the full explanatory power of the model (as opposed to the interaction term alone), we utilize a two degree-of-freedom test that jointly evaluates both SNP main effects and potential SNP x AOS interactions (Kraft et al. 2007).
