ADHD: strategies to unravel its genetic architecture.

Attention deficit/hyperactivity disorder (ADHD) is a common and impairing neuropsychiatric disorder with onset at preschool age and strong persistence over time. Its validity as a psychiatric disorder has been established according to Robins and Guze criteria. Genetic factors predominate in the etiology of ADHD. This paper summarizes the current status of genetic research into ADHD, and describes eight factors that complicate research into genetically complex disorders as ADHD. These factors are that multiple genes of small main effects are involved rather than main genes, the relevant phenotype is unknown, presence of clinical heterogeneity, presence of genetic heterogeneity, gene-environment correlation, gene-environment interaction, importance of endophenotypes, and importance of developmental factors. The further unraveling of the genetic architecture of ADHD will depend to a large extent on how well these complicating factors are handled or even used.