Genetic Analysis of Attention Deficit Hyperactivity Disorder (ADHD)

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common childhood disorders and the most common childhood neurodevelopmental behavioral disorder. Symptoms include difficulty staying focused (inattention), difficulty controlling behavior (impulsivity), and hyperactivity. Symptoms typically develop between six and 12 years of age, and frequently persist into adulthood, with serious life-long health and social consequences. Affected children are at increased risk for poor educational achievement, low income, underemployment, legal difficulties, and impaired social relationships. The general belief is that ADHD is caused by a combination of genetic and environmental factors. The main objective of the study is to conduct genetic and behavioral studies that will closely characterize the genetic influences in diagnosis, prognosis, severity, and pharmacological response in ADHD patients. Since the start of the study in 2000, research has contributed to the understanding of the innate susceptibility of ADHD and associated comorbidities; the interaction of genetic, demographic, and environmental factors underpinning the risk of developing ADHD; the extent to which these factors shape the response of ADHD patients to pharmacological interventions (pharmacogenetics); the over-representation of functional and ontological genebased networks implicated in determining synapse structure; and the use of advanced geneticepidemiological models with potential for use in clinical practice (translational genomics). The most significant research finding occurred in 2010, when the study team identified LPHN3, a key gene involved in the etiology of ADHD and comorbid conditions in one of the previously identified regions of strong genetic signal in chromosome 4q13.2. In order to provide power for the study s statistical analyses, the upper enrollment goal is 4,000 participants. Although the study has several small and genetically distinct cohorts, the majority of subjects come from the United States of America population through outreach recruitment efforts. Recruitment has been very successful and the large cohort numbers provide support for identification of genetic components related to the diagnosis of ADHD. Recent efforts have focused on identifying new areas of the genome associated with ADHD, and identifying genetic (coding and non-coding) variations implicated in the etiology and clinical manifestations of ADHD. A primary aim of the study is to correlate genetic and biological markers for diagnosis and prognosis of ADHD identified through the use of state of the art genomics, which includes enome-wide association studies, linkage analysis, whole genome and exome sequencing, and targeted gene capture in cosmopolitan and isolated populations. As the current diagnosis of ADHD is based on subjective observations, one of the main goals of the study is to develop a more definitive system to diagnose ADHD and to assess and predict prognosis.