Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood-onset psychiatric disorders afflicting 5-10 percent of children and adolescents, and 2 percent or more of all adults. Twin, family, and adoption studies support a significant role for genetic influences in ADHD. The heritability of ADHD is 70-80 percent and patterns in families suggest that a major autosomal gene may contribute to the genetic effect. The purpose of the present study is to identify susceptibility genes underlying ADHD through a genome search and linkage disequilibrium studies in 300 Affected Sibling Pair (ASP) families. The long-term goal of this research is to understand the genetic etiology of ADHD. Understanding the genetic basis of ADHD will enable more accurate diagnosis and treatment of preventive measures, tailored to the specific genetic susceptibility of an individual, to be developed. Based upon a year of extensive pilot research, and in collaboration with the Wellcome Trust Centre for Human Genetics at Oxford University, the present study is proposed to: 1. Identify susceptibility gene locations in ADHD through a systematic genome scan in 300 Affected Sibling Pair (ASP) families - specifically to test the hypothesis that a gene or genes of major effect underlie ADHD. 2. Identify susceptibility genes underlying the clinical and cognitive manifestations of ADHD through the linkage disequilibrium studies of candidate genes involved in dopamine transmission, for example, to test the hypothesis that the dopamine transporter gene influences behavioral symptoms of impulsivity and hyperactivity and not behavioral symptoms of inattention. 3. Identify the modifying role sex has in the expression of ADHD susceptibility genes -specifically to test the hypotheses that a gene located on the X chromosome modifies ADHD expression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH058277-02
Application #
2883467
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Moldin, Steven Owen
Project Start
1998-03-15
Project End
2003-02-28
Budget Start
1999-03-01
Budget End
2000-02-29
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Other Domestic Higher Education
DUNS #
119132785
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 :
Yang, Li; Neale, Benjamin M; Liu, Lu et al. (2013) Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: genome-wide association study of both common and rare variants. Am J Med Genet B Neuropsychiatr Genet 162B:419-430
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
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
Neale, Benjamin M; Medland, Sarah E; Ripke, Stephan et al. (2010) Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 49:884-97
Hale, T Sigi; Smalley, Susan L; Walshaw, Patricia D et al. (2010) Atypical EEG beta asymmetry in adults with ADHD. Neuropsychologia 48:3532-9
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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