A Genome-wide Association Study on the Endophenotype of Spatial Working Memory in ADHD
Condition: Attention-deficit/Hyperactivity Disorder
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Study type: Observational

Summary: 
      Specific Aims:

        1. To find the genetic variations associated with spatial working memory performance in
           patients with ADHD by using genome-wide association studies (GWAS);

        2. To find the genetic variations associated with spatial working memory performance in
           healthy subjects by using GWAS;

        3. To recruit a validation sample and to replicate the findings from the initial GWAS;

        4. To test whether genetic variations significantly associated with spatial working memory
           are also associated with ADHD.
    

Detailed description: 
      Attention deficit hyperactivity disorder (ADHD), characterized by inattention, hyperactivity
      and impulsivity, is an early onset, highly heritable, clinically heterogeneous, long-term
      impairing disorder with tremendous impact on individuals, families, and societies. Our
      research team has conducted a series of biological studies on spatial working memory deficits
      of ADHD, and substantial evidence has suggested spatial working memory deficits as the
      important neuropsychological biomarker with translational values and favorable endophenotypic
      properties for ADHD. Despite the abundance of molecular genetic studies on ADHD, the genetic
      etiologies of ADHD have been non-conclusive. Because genetic studies on endophenotypes can
      offer more information on genetic and brain process, endophenotypic approach can efficiently
      enhance the statistical power and make genome-wide association studies (GWAS) applicable in
      much smaller sample. To date, there has been no GWAS study on spatial working memory deficits
      of ADHD.

      This is a 3-year project. Our previous studies have collected blood samples and spatial
      working memory data of 382 patients with ADHD and 150 healthy subjects. In this 3-year
      project, we will recruit 232 healthy subjects, aged 7-18 years. The measures include (1)
      interviews for psychopathology (K-SADS-E), (2) questionnaires to measures ADHD symptoms
      (SNAP-IV), and (3) neuropsychological tests: Spatial Working Memory task of the CANTAB. In
      the first year, a case-only GWAS on spatial working memory (n = 254) will be conducted. In
      the second year, a control-only GWAS on spatial working memory (n = 254) will be conducted.
      In the third year, findings from the initial two GWAS will be replicated in a validation
      sample composed of 128 patients with ADHD and 128 healthy controls.

      By careful calculation, a sample size of 382 ADHD subjects will provide adequate power to
      detect genome-wide significant genetic variations and replicate the findings in an
      independent validation sample. We anticipate to identify the relationship between genetic
      variations of ADHD and the endophenotype of spatial working memory. Our findings will
      significantly contribute to our understanding of the pathophysiological mechanisms of ADHD,
      especially the pathological pathway from genes, through endophenotype, to behavioral
      phenotypes.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        The existing sample is composed of 382 children withADHD and 150 healthy subjects. We plan
        to recruit additional 232 healthy subjects (104 in the first year; 128 in the second year),
        aged 7 to 18 years.
      
Biospecimen description: 
      15 ml blood will be withdrawn from the subjects (one heparin-rinsed tube for cell culture,
      one EDTA rinsed tube for DNA extraction)