Failure to replicate an excess of the long dopamine D4 exon III repeat polymorphism in ADHD in a family-based study

The DRD4 exon III repeat polymorphism has been associated in adults with Novelty Seeking personality traits and in children with attention deficit hyperactivity disorder (ADHD) in some but not all studies. In a previous report we failed to observe preferential transmission of the long DRD4 repeat in ADHD compared to the haplotype relative risk (HRR) derived control group in a group of 49 triads (both parents and ADHD child) recruited in the Jerusalem area. In the current study we independently recruited an additional group of 49 triads from a different geographical location (Petak Tikvah) in Israel but having a similar ethnic background. In contrast to previous findings from a number of groups, in the current study an excess of the long DRD4 alleles was observed in the HRR control group compared to the ADHD subjects (Likelihood ratio = 5.50, P = 0. 02). In the expanded Israeli group of 98 triads so-far examined for the DRD4 repeat polymorphism there is an excess of the long alleles in the HRR control group (Likelihood ratio = 3.81, P = 0.05). These results attest to the complexity of ADHD inheritance and the likelihood that genetic heterogeneity characterizes this disorder especially across ethnic and cultural boundaries.