Epistatic interaction between COMT and DTNBP1 modulates prefrontal function in mice and in humans.

ABSTRACT: Cognitive functions are highly heritable and the impact of complex genetic interactions, though undoubtedly important, has received little investigation. Here we show in an animal model and in a human neuroimaging experiment a consistent non-linear interaction between two genes--catechol-O-methyl transferase (COMT) and dysbindin (dys; dystrobrevin-binding protein 1 (DTNBP1))--implicated through different mechanisms in cortical dopamine signaling and prefrontal cognitive function. In mice, we found that a single genetic mutation reducing expression of either COMT or DTNBP1 alone produced working memory advantages, while, in dramatic contrast, genetic reduction of both in the same mouse produced working memory deficits. We found evidence of the same non-linear genetic interaction in prefront

SUBMITTER: Papaleo F 

PROVIDER: S-EPMC4845721 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature