Animal studies provide very important contributions to understanding the molecular basis of human diseases and traits. However, similar to what is recognized by the National Advisory Mental Health Council Workgroup on Genomics for other psychiatric disorders178, we argue that there is no “probably-true” animal model mapping directly onto human SUDs. Psychiatric and behavioural traits appear to have a genetic architecture even more polygenic than other complex traits due to the action of two main forces: background selection and diagnostic heterogeneity179, 180. Both of these mechanisms are human-specific and we believe it is problematic to model them in animals. These limitations should be recognized when using animal models to investigate SUD pathogenesis. The utility of animal models for evaluating the biological properties and effects of genes and specific variants that were first identified in human studies is widely accepted, and an important method in understanding genetic phenomena identified in human subjects. On balance we believe that the utility of animal studies for complex behavioural traits like SUD risk in humans, is mostly limited to evaluation and testing of findings from humans, rather than in enhancing gene discovery for human traits (that are not necessarily congruent to animal traits).
