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Transmission disequilibrium studies in early onset of obsessive-compulsive disorder for polymorphisms in genes of the dopaminergic system


Walitza, S; Scherag, A; Renner, T J; Hinney, A; Remschmidt, H; Herpertz-Dahlmann, B; Schulze, E D; Schafer, H; Lange, K W; Wewetzer, C; Gerlach, M (2008). Transmission disequilibrium studies in early onset of obsessive-compulsive disorder for polymorphisms in genes of the dopaminergic system. Journal of Neural Transmission, 115(7):1071-1078.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:July 2008
Deposited On:14 Feb 2009 21:14
Last Modified:05 Apr 2016 13:00
Publisher:Springer
ISSN:0300-9564
Publisher DOI:10.1007/s00702-008-0051-6
PubMed ID:18446263
Permanent URL: http://doi.org/10.5167/uzh-13679

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