Among the most heavily studied polymorphisms in all of psychiatric genetics is the so-called warrior/worrier Val158Met amino acid substitution caused by rs4680, which was first described by Lachman et al. (1996). This SNP appears to alter the enzymatic activity of COMT such that Met carriers have lower activity. This polymorphism has been associated with numerous diseases and putative intermediate phenotypes, including pain sensitivity, anxi ety and substance abuse (Tunbridge. 2010; Bousman et al. 2009). To clarify the importance of the coding SNP versus polymorphisms that might be in LD with rs4680, Papaleo et al. (2008) generated mice that were transgenic for the human Val allele of COMT. Presence of the Val allele altered the effects of amphetamine on working memory tasks in a manner that paralleled earlier observations in humans (Mattay et al. 2003).
