Yet, there is also evidence that multiple common variants can begin to explain more of genetic variation in addiction. For smoking behavior, for example, we know that individual genetic variants contribute only a small effect to the development of nicotine dependence. Yet in combination, these genetic factors play a substantial role in the development of heavy smoking. For example, in our study from the Collaborative Genetic Study of Nicotine Dependence, approximately 9 variants in the nicotinic receptors explain 5% of the phenotypic variance in the sample (Saccone et al., 2010b). Though this explained variance estimate is likely higher than what will be seen in a general population study of smoking behavior, it demonstrates that collectively common genetic polymorphisms of small effect can begin to explain a larger proportion of genetic variation related to disease. Most likely hundreds, and more probably thousands, of genetic variants will be required to explain the genetic input to disease.
