COMT and DRD3 polymorphisms, environmental exposures, and personality traits related to common mental disorders

In a community sample of 2,327 Caucasians, we tested the hypotheses that po lymorphisms in the COMT and DBD3 genes are associated with personality trai ts conferring vulnerability to anxiety, depression, or alcohol misuse, or w ith current symptoms of these; and that the association is stronger in pers ons who also have been exposed to stressor experiences. To conserve resourc es and to allow replication, the genetic analysis was undertaken in two sta ges. For the COMT polymorphism, no statistically significant associations w ere found in the first sample of 862 persons. The remainder of the sample w as therefore not analysed for that gene. For the DRD3 polymorphism, those i n the first sample with at least one of the Ser(9) alleles had significantl y higher scores in neuroticism (p=0.006) and behavioral inhibition (p=0.003 ). There was a trend, failing to meet the 1% significance criterion, for th ose with this genotype also to have higher depression and anxiety. The grou ps did not differ in alcohol use. In persons with the Ser(9) allele who wer e also exposed to stressors, there was a higher level of depression at the 5% level; and the depression level was higher in homozygotes. But when the remainder of the sample (1,465) was analysed, none of the associations reac hed statistical significance. We conclude that neither the COMT nor DRD3 po lymorphisms are associated with anxiety, depression, or alcohol abuse. Am. J. Med. Genet. (Neuropsychiatr, Genet.) 96:102-107, 2000 (C) 2000 Wiley-Lis s, Inc.