A Family Based Association Study of DRD4, DAT1, and 5HTT and Continuous Traits of Attention-Deficit Hyperactivity Disorder

• Published in: Behavior genetics Vol. 41; no. 1; pp. 165 - 174
• Main Authors: Bidwell, L. Cinnamon, Willcutt, Erik G., McQueen, Matthew B., DeFries, John C., Olson, Richard K., Smith, Shelley D., Pennington, Bruce F.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 2011; Springer Nature B.V
• Subjects: Anxiety Disorders - diagnosis; Anxiety Disorders - genetics; Attention Deficit and Disruptive Behavior Disorders - diagnosis; Attention Deficit and Disruptive Behavior Disorders - genetics; Attention Deficit Disorder with Hyperactivity - diagnosis; Attention Deficit Disorder with Hyperactivity - genetics; Attention deficit hyperactivity disorder; Behavior; Behavioral Science and Psychology; Child; Clinical Psychology; Comorbidity; Conduct Disorder - diagnosis; Conduct Disorder - genetics; Depressive Disorder, Major - diagnosis; Depressive Disorder, Major - genetics; Diseases in Twins - genetics; Dopamine; Dopamine Plasma Membrane Transport Proteins - genetics; Family based; Female; Gene Frequency; Genes; Genetic Association Studies; Genotype; Genotype & phenotype; Health Psychology; Heritability; Humans; Hyperactivity; Male; Original Research; Phenotype; Phenotypes; Phobic Disorders - diagnosis; Phobic Disorders - genetics; Psychology; Psychopathology; Public Health; Receptors, Dopamine D4 - genetics; Serotonin Plasma Membrane Transport Proteins - genetics; Symptoms; United States > US; Genetic; ADHD; Dopamine; Serotonin; FBAT
• ISSN: 0001-8244; 1573-3297
• DOI: 10.1007/s10519-010-9437-y

Despite its high heritability, genetic association studies of attention deficit-hyperactivity disorder (ADHD) have often resulted in somewhat small, inconsistent effects. Refining the ADHD phenotype beyond a dichotomous diagnosis and testing associations with continuous information from the underlying symptom dimensions may result in more consistent genetic findings. This study further examined the association between ADHD and the DRD4, DAT1, and 5HTT genes by testing their association with multivariate phenotypes derived from continuous measures of ADHD symptom severity. DNA was collected in 202 families consisting of at least one ADHD proband and at least one parent or sibling. VNTR polymorphisms of the DRD4 and DAT1 genes were significantly associated with the continuous ADHD phenotype. The association with DRD4 was driven by both inattentive and hyperactive symptoms, while the association with DAT1 was driven primarily by inattentive symptoms. These results use novel methods to build upon important connections between dopamine genes and their final behavioral manifestation as symptoms of ADHD.