No single approach to designing genome wide association studies or to analyzing genome wide association data is now universally accepted. There is now no universal standard for considering genome-wide association results “significant” in ways that allow us to identify polygenic allelic variants in reasonably-sized single experiments. Here, we describe specific sets of working hypotheses about the genetic architecture of addiction (eg vulnerability to develop dependence on an addictive substance). This set of hypotheses is also useful for considering the molecular genetic bases for other common, complex phenotypes that, like addictions, display both substantial evidence for heritability and little evidence for large influences from any single gene (eg single gene, Mendelian influences or oligogenic effects that come from a few genetic loci, each with moderate effects on the phenotype). We then detail experimental design and analytic approaches that arise from working hypotheses about underlying genetic architecture and likely sources of false positive results.
