It is likely that, as for most complex diseases, alcohol dependence and AUDs are due to variations in hundreds of genes, interacting with different social environments. An additional challenge in the search for genetic variants that affect the risk for AUDs is that there is extensive clinical heterogeneity among those meeting criteria. Because the diagnosis of an AUD requires the presence of a set of symptoms from a checklist, there are many different ways one could meet the criteria. There are 35 different ways one could pick 3 criteria from 7 (DSM-IV alcohol dependence) and 330 ways to pick 4 from 11 (DSM-5 severe AUD). The clinical heterogeneity likely reflects the genetic heterogeneity of the disease. The difficulties of genetic studies are compounded by environmental heterogeneity in access to alcohol and social norms related to drinking.
