Attention-Deficit Hyperactivity Disorder in the post-genomic era

BACKGROUND: ADHD is a common and complex genetic disorder. Genetic risk factors are expected to be multiple, have small effect sizes when considered individually and to interact with each other and with environmental factors. OBJECTIVE: To describe the difficulties involved in the genetic investigation of such a complex disorder and give a prospective for the future. METHODS: Review based on empirical literature and project description. RESULTS: Considerable progress has been achieved through the association analysis of candidate gene loci. Linkage scans using affected sibling pairs have identified a number of potential loci that may lead to the identification of novel genes of moderate effect size. Quantitative trait locus (QTL) approaches provide powerful complementary strategies that have the potential to link the categorical disorder to continuously distributed traits associated more closely with underlying genetic liability in the general population. Success in identifying some associated genes has been complemented by functional studies that seek to understand the mode of action of such genes. CONCLUSION: Progress in understanding the mechanisms involved has not been straightforward and many inconsistencies have arisen. In order to take advantage of the potential for progress that stems from the genetic findings it will be important to draw upon a variety of approaches and experimental paradigms. A functional genomic approach to ADHD means that investigation of gene function is carried out at various levels of analysis, not only at the level of molecular and cellular function but also at the level of psychological processes, neuronal networks, environmental interactions and behavioural outcomes