Genetic Analysis of Attention Deficit Hyperactivity Disorder (ADHD)
Condition: ADHD
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Study type: Observational

Summary: 
      Attention Deficit Hyperactivity Disorder (ADHD) is the most common behavioral disorder in
      childhood, affecting 3-5% of children between the ages of 7 and 17. Family studies suggest
      that there is a genetic component to ADHD. Scientists believe that it is a complex disorder
      in which two or more genes may be involved.

      Potentially eligible families will be asked to give written consent to participate and will
      be asked to complete questionnaires for each member in the family. In addition, an interview
      will be administered to the parent of minors enrolled in the study to determine their
      eligibility for being in the study. This screening tool is computerized and will take
      approximately 45 minutes to administer per child.

      Once screenings are completed, a blood collection kit will be sent to the family to take to
      their local medical care provider, have blood samples drawn and sent to NIH. There is no cost
      to the family to participate. We would like to enroll entire families, with both parents and
      all children.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        1. Families with children, seven through 17 years of age, diagnosed with ADHD (defined as
        the proband for the study). 2. The probands siblings, either affected with ADHD
        (concordant) or unaffected (discordant), seven years of age and above, including adult
        siblings. 3. The parents, both mothers and fathers, of enrolled probands.
      
Keywords: Linkage; Gene Identification; Hyperactivity; Natural History; Attention Deficit Hyperactivity Disorder; ADHD