The role of catechol-O-methyltransferase (COMT) val158met in prefrontal cortical deficits associated with the liability to schizophrenia remains controversial. This study evaluated 464 healthy adult participants using three measures of executive functions in working memory: a 3-back version of the N-back continuous performance task (CPT) and two variants of the AX-CPT. The interpretability of N-back performance was confounded by possible generalized deficits, whereas the AX variants included internal controls for uncovering specific deficits. There was no relationship between the COMT genotype and N-back performance, whereas val/val individuals had a specific deficit on a dot-pattern version of the AX-CPT. In this case, a specific executive function known as context processing appeared to be compromised. These data suggest that the interpretability gained by including task manipulations to uncover specific deficits can enhance associations between cognitive and genetic levels of analysis.