The noradrenergic system has been implicated in arousal, vigilance, irritability hostility, and memory. This suggests the hypothesis that genetic variants at noradrenergic receptors may be risk factors of these behaviors. To test this hypothesis, the potential association between measures of these traits and genetic variation at the adrenergic(2A) receptor gene (ADRA2A), using a common single nucleotide polymorphism (SNP) polymorphism of the promoter region, were examined in two independent sets of subjects: university students (student group), and parents of twins in the Minnesota Twin Study (twin group). In the student group, there was a significant linear association by genotype (11 > 12 > 22) for the total Brown ADD score (BADD), and BADD subscores of memory and irritability, and with the total Buss-Durkee Hostility Inventory (BDHI) score and BDHI subscores of indirect hostility, irritability, negativity, and verbal aggression. A multiple analysis of variance (MANOVA) of all the BADD and BDHI subscores was significant at P ≤ 0.009. For the twin group, the same genotype associations were significant for the Multidimensional Personality Questionnaire (MPQ) impulsivity scores but not for the MPQ aggression or harm avoidance scores. The ADRA2A gene accounted for 1.8-8.3% of the variance of these scores. (C) 2000 Lippincott Williams and Wilkins.