| Attention-deficit/hyperactivity disorder (ADHD) is a pervasive neurobehavioral disorder affecting ∼5% of children and adolescents and ∼3% of adults. As part of an ongoing study into the molecular genetics of ADHD, we have made considerable progress towards the identification of the effect loci underlying susceptibility. We have conducted the most extensive linkage study in ADHD to date, and have defined 4 genomic regions presenting significant evidence of linkage. While two regions have been replicated in independent population samples, joint analysis of combined linkage data suggests genetic heterogeneity across samples. Novel statistical analyses yield striking evidence of sex-specific effect alleles within our sample, and indicate genetic loading within the serotonin neurotransmission pathway underlies susceptibility to ADHD. Ongoing association studies have identified candidate genes yielding significant evidence of association, and have narrowed the search for common effect alleles contributing to the etiology of ADHD. In totality, we have set the stage for focused association studies that will eventually define major genetic components of ADHD, and elucidate the causal biological mechanisms. |
