title: Phenotype studies of the DRD4 gene polymorphisms in ADHD: association with oppositional defiant disorder and positive family history.
abstract: The objective of this study was to investigate association of DRD4 polymorphisms with ADHD subtypes for which there is evidence for increased heritability. The genetic variants tested were the 120 bp insertion/deletion, the -616, -521, -376, and the 48 bp DRD4 VNTR. The primary analyses were of association with oppositional defiant disorder (ODD), conduct disorder (CD), and diagnostic subtypes. Secondary analyses of clinical subtype were exploratory in nature and included analysis of association of DRD4 polymorphisms with family history of ADHD. We observed significant association between DRD4 7-repeat allele transmission and ADHD children with comorbid ODD (chi(2) = 6.74, df = 1, P = 0.01, OR = 2.45) The DRD4 7-repeat allele was also significantly associated with family history positive ADHD (chi(2) = 10.12, df = 1, P = 0.0021, OR = 3.57). We observed no significant distortion in the transmission of any of the tested DRD4 variants with inattentive or hyperactive-impulsive subtypes or symptom dimensions. In conclusion, our findings of increased DRD4 7-repeat allele transmission in ODD extend those reported by Holmes et al. To our knowledge, this is the first study to report association of the DRD4 7-repeat allele with ADHD children who have a positive family history of ADHD. Overall, the results from this study support the investigation of clinical subtypes in molecular genetic studies of ADHD.
authors.affiliation: Departments of Psychiatry and Genetics, Trinity College Dublin, Dublin, Ireland.
authors.forename: Aiveen
authors.initials: A
authors.lastname: Kirley
authors.forename: Naomi
authors.initials: N
authors.lastname: Lowe
authors.forename: Celine
authors.initials: C
authors.lastname: Mullins
authors.forename: Mary
authors.initials: M
authors.lastname: McCarron
authors.forename: Grainne
authors.initials: G
authors.lastname: Daly
authors.forename: Irwin
authors.initials: I
authors.lastname: Waldman
authors.forename: Michael
authors.initials: M
authors.lastname: Fitzgerald
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Ziarih
authors.initials: Z
authors.lastname: Hawi
mesh_terms: D000328:Adult; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000473:pathology; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000235:genetics / Q000473:pathology; D002648:Child; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4
chemical_list: C493599:DRD4 protein, human; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4