Dopamine transporter polymorphism associated with externalizing behavior problems in children

Early childhood externalizing behavior is a stable and heritable pattern of aggressive and delinquent behavior that often leads to the development of serious psychiatric disorders such as conduct disorder and attention deficit hyperactivity disorder. We examined the relationship between parent reported externalizing behavior (assessed at ages 4, 7, and 9 years) and the VNTR polymorphism of the 3' untranslated region of SLC6A3 (DAT1) in a community sample of 790 children ascertained as part of our longitudinal twin and adoption studies. We applied the sibling-based methodology developed by Fulker et al. 1999: Am J Hum Genet 64:259-267 for estimating allelic association with quantitative traits, while controlling for population stratification. An extension of these methods allowed for the inclusion of monozygotic twins, dizygotic twins, siblings, and singletons. We have demonstrated that the 9-repeat variant of the DAT1 is a significant risk allele for externalizing behavior at ages 4 (P=0.001) and 7 years (P=0.02). Although the effect size was negligible at age 9 (P=0.92), a formal test of the developmental decrease in effect across the three ages was non-significant (P=0.70).