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.
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