title: Transmission disequilibrium studies in early onset of obsessive-compulsive disorder for polymorphisms in genes of the dopaminergic system.
abstract: The dopaminergic system has been shown to be involved in the aetiology of obsessive-compulsive disorder (OCD). Family studies suggest a higher genetic loading in patients with early onset OCD. Our investigation is the first family-based association study concerning polymorphisms in genes of the dopaminergic system in early onset OCD. We studied polymorphisms within the dopamine-4 receptor gene (DRD4), the dopamine transporter gene (DAT1) and the catecholamine-O-methyltransferase gene (COMT). Associations of alleles of DRD4 and COMT with OCD have previously been reported in adults, while a trend towards an association was found for DAT1 alleles. In our study we observed transmission disequilibrium for the 48-bp repeat polymorphism of the DRD4 gene using the ETDT (P=0.047) in 69 trios comprising patients with early onset OCD and both of their parents. Post hoc TDT analysis of the DRD4 showed reduced transmission of the 4-repeat allele and a slightly increased transmission rate for the 7- and the 2-repeat allele. No evidence of transmission disequilibrium was detected for alleles of the DAT1 and COMT polymorphisms. These polymorphisms do not appear to play a major role in the genetic predisposition to early onset OCD in our study group.
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany. walitza@kjp.uni-wuerzburg.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Walitza
authors.forename: André
authors.initials: A
authors.lastname: Scherag
authors.forename: Tobias J
authors.initials: TJ
authors.lastname: Renner
authors.forename: Anke
authors.initials: A
authors.lastname: Hinney
authors.forename: Helmut
authors.initials: H
authors.lastname: Remschmidt
authors.forename: Beate
authors.initials: B
authors.lastname: Herpertz-Dahlmann
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schulz
authors.forename: Helmut
authors.initials: H
authors.lastname: Schafer
authors.forename: Klaus W
authors.initials: KW
authors.lastname: Lange
authors.forename: Christoph
authors.initials: C
authors.lastname: Wewetzer
authors.forename: Manfred
authors.initials: M
authors.lastname: Gerlach
mesh_terms: D000293:Adolescent; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D011110:Polymorphism, Genetic; D050638:Receptors, Dopamine D4 / Q000235:genetics*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; D002394:Catechol O-Methyltransferase