title: A family based association study of DRD4, DAT1, and 5HTT and continuous traits of attention-deficit hyperactivity disorder.
abstract: 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.
authors.affiliation: Department of Psychiatry and Human Behavior, Brown University, Box G-S121-4, Providence, RI 02912, USA. cinnamon_bidwell@brown.edu
authors.forename: L Cinnamon
authors.initials: LC
authors.lastname: Bidwell
authors.forename: Erik G
authors.initials: EG
authors.lastname: Willcutt
authors.forename: Matthew B
authors.initials: MB
authors.lastname: McQueen
authors.forename: John C
authors.initials: JC
authors.lastname: DeFries
authors.forename: Richard K
authors.initials: RK
authors.lastname: Olson
authors.forename: Shelley D
authors.initials: SD
authors.lastname: Smith
authors.forename: Bruce F
authors.initials: BF
authors.lastname: Pennington
mesh_terms: D001008:Anxiety Disorders / Q000175:diagnosis / Q000235:genetics; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000235:genetics*; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000175:diagnosis / Q000235:genetics; D002648:Child; D015897:Comorbidity; D019955:Conduct Disorder / Q000175:diagnosis / Q000235:genetics; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics; D004200:Diseases in Twins / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D010698:Phobic Disorders / Q000175:diagnosis / Q000235:genetics; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D050638:Receptors, Dopamine D4