Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable and common childhood-onset psychiatric disorder that poses a significant burden to the individual and society in terms of educational, psychological, and medical costs. There is substantial variability in ADHD including high rates of reading disability (20%) and psychiatric disorders (60%). Despite the availability of relatively efficacious medication intervention (i.e. stimulants), variability in treatment response is substantial and there remains significant morbidity associated with ADHD including poor educational outcome, high risk for accidents and substance abuse, poor social functioning, academic and occupational failure, and lifelong suffering from co-morbid psychiatric disorders. Given the impairing nature of ADHD, our long-term goal is to identify the specific genes underlying liability to this disorder and associated co-morbidities, develop early methods for detection of 'at risk' individuals, and design early interventions that are individually tailored to minimize the impairment associated with ADHD. As a first step in achieving this goal, identification of the underlying genetic risk alleles and their role in the brain is crucial. In the first 5-year period of funding, we significantly moved toward completion of the first step by collecting data on over 300 Affected Sibling Pairs (ASPs) with ADHD and completing a genome-wide scan to identify chromosomal locations of risk genes in ADHD. Several chromosome regions are indicated to harbor risk genes and our proposed competitive 5-year renewal has the following Specific Aims: 1) increase the sample size to 600 ASPs and contribute DNAs to an NIMH cell line repository for DNA sharing; 2) to replicate, rank and refine chromosomal regions harboring risk genes in ADHD using dense marker sets (2 cM) and linkage studies in the current set of 300 ASPs and the new set of 300 ASPs; and 3) to use phenotypes associated with ADHD and familial in the ASPs to reduce locus heterogeneity and increase the signal to noise ratio in linkage studies. Successful completion of these specific aims will lay the foundation for determining where to look for specific risk genes using SNP/association methodologies as well as identifying potential gene to brain pathways in ADHD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH058277-10
Application #
7425114
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Lehner, Thomas
Project Start
1998-03-15
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2010-04-30
Support Year
10
Fiscal Year
2008
Total Cost
$602,660
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Loo, Sandra K; McGough, James J; McCracken, James T et al. (2018) Parsing heterogeneity in attention-deficit hyperactivity disorder using EEG-based subgroups. J Child Psychol Psychiatry 59:223-231
Morgan, Julia E; Lee, Steve S; Loo, Sandra K (2016) Fluid Reasoning Mediates the Association of Birth Weight With ADHD Symptoms in Youth From Multiplex Families With ADHD. J Atten Disord :
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Loo, Sandra K; Shtir, Corina; Doyle, Alysa E et al. (2012) Genome-wide association study of intelligence: additive effects of novel brain expressed genes. J Am Acad Child Adolesc Psychiatry 51:432-440.e2
Hinney, Anke; Scherag, André; Jarick, Ivonne et al. (2011) Genome-wide association study in German patients with attention deficit/hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet 156B:888-97
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Hale, T Sigi; Smalley, Susan L; Walshaw, Patricia D et al. (2010) Atypical EEG beta asymmetry in adults with ADHD. Neuropsychologia 48:3532-9
Hale, T Sigi; Smalley, Susan L; Dang, Jeff et al. (2010) ADHD familial loading and abnormal EEG alpha asymmetry in children with ADHD. J Psychiatr Res 44:605-15
Loo, Sandra K; Hale, Sigi T; Hanada, Grant et al. (2010) Familial clustering and DRD4 effects on electroencephalogram measures in multiplex families with attention deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 49:368-77
Smalley, Susan L; Loo, Sandra K; Hale, T Sigi et al. (2009) Mindfulness and attention deficit hyperactivity disorder. J Clin Psychol 65:1087-98

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