In conclusion we have performed the first GWAS of the subjective response to a drug of abuse and identified two interesting associations. CDH13 has previously been associated with a number of substance abuse and other psychiatric phenotypes and is also supported by data from knock-out mice. Replication in independent datasets will be important to establish the role of CDH13 in drug addiction, and to determine the extent to which initial drug responses are related to the etiology of addiction. SRD5A1 is similarly supported by prior evidence including corroborating genetic studies, gene expression and enzymatic activity data, but the lack of replication of this result is a cause for concern. We were motivated to perform this study using a relatively modest sample size because we believed that intermediate pharmacogenomic phenotypes might be influenced by alleles that contribute a larger fraction of the genetic variance. This study reflects both the utility and challenges of such phenotypes for discovery and enrichment of our understanding of complex psychiatric constructs such as drug abuse.
