An additional potential drawback to GWAS studies is that there is heterogeneity of study design which may obscure true genetic contributors to disease, and careful consideration in the design of future addiction GWAS studies may help to alleviate this issue. An example is seen in the comparison of our study (Collaborative Genetic Study of Nicotine Dependence – COGEND) designed to examine genetic influences on smoking behavior and nicotine dependence, and the large scale GWAS of smoking (Saccone et al., 2009, 2010b; Thorgeirsson 2010). Our COGEND study compared very light smokers and current nicotine dependent smokers, thus focusing on differences between those who can smoke a little and not become addicted and individuals with addiction. In addition, our sample recruited subjects using a systematic strategy and in a relatively narrow age range (25–44) to avoid the confounding of secular trends in smoking. Conversely, the large scale GWAS of smoking were based on current and former smokers, and the entire range of smoking amount was included. The age range in these studies encompassed different generations in which we know smoking behavior has changed. In addition, some subjects were recruited for lung cancer, others for heart disease, and many other medical illnesses.
