For example, Tan et al. [62] reported an apparent epistatic interaction between the catechol-O-methyltransferase (COMT) gene and the metabotropic glutamate receptor mGluR3 (GRM3) gene on the engagement of the prefrontal cortex during working memory, indicating an epistatic effect of these two genes in human cortical circuits that have been implicated in the working memory dysfunction that is observed in schizophrenia. This evidence concerns the gene COMT and schizophrenia.