In contrast to the simple effects of smoking, the effects of CP and obesity were complex. Their interaction is shown most clearly in Analysis Set #3 which was limited to 110 European-American subjects. The analysis demonstrated a synergism between these two factors in delaying the P300a component. The interaction was duplicated (Figure 2) when a GABRA2 genotype previously associated with conduct problems was substituted for the CP factor. At least two interpretations for the interaction can be offered. The first interpretation hypothesizes that a GABRA2 genotype, associated with conduct problems in previous studies, decreases the age-of-onset or increases the duration of obesity. As a result, the genotype potentiates the adverse effects of obesity on frontal white matter, and delays the emergence of this frontally-generated P300 component. The alternative interpretation views obesity, conduct problems, and increased P300a latency (i.e., frontal brain dysfunction) as behavioral or neurophysiological expressions of a common genetic diathesis involving GABRA2.
