| Attention Deficit Hyperactivity Disorder (ADHD) is among one of the most common childhood onset emotional-behavioral disorders. ADHD is a highly heritable disorder affecting between 7-8% of children and occurs more frequently in boys than girls. Twin and adoption studies have estimated the heritability of ADHD at anywhere between 70-80%. In addition, ADHD can persist into adulthood with prevalence estimates of approximately 4% in adults from the United States. In order to understand the role genetics plays in the susceptibility of ADHD, we sought to identify genetic determinants that contribute risk for the disorder. The first aim of this project was to complete a candidate gene study using an ADHD sample population designated the Vermont Family Study. The Vermont Family Study is a collection of 783 individuals from 207 families each containing at least one child with the disorder. Each individual was genotyped for 41 different polymorphisms in 27 different genes. The resulting genotypes are analyzed for statistical associations to many different phenotypes ranging from aggression, IQ, and attention problems. Interestingly, three novel alleles in the serotonin transporter promoter were identified in these samples that have not been reported in the literature. Experiments were designed to functionally characterize these novel alleles and understand the role this promoter polymorphism plays in the expression of this receptor protein. The second aim of this study was to perform a genome-wide association study in an independent sample of 4,795 Dutch Twins, their siblings, and parents using the Affymetrix SNP6.0 microarray. Single Nucleotide Polymorphism (SNP) and Copy Number Variation (CNV) data were generated from each DNA sample using a high-density microarray able to detect 1.8 million markers evenly distributed across the whole genome. The data is currently being analyzed to identify polymorphisms associated with ADHD and many other important phenotypes. We were able to identify CNVs in monozygotic twins that are putatively associated with ADHD. Additionally, we also show that individuals with attention problems have larger CNVs that overlap with genes. Finally, CNVs were shown to be highly similar between two different tissue derived DNAs (blood and buccal) for the same individual and between monozygotic twin pairs. |
