Modification of the association between early adversity and obsessive-compulsive disorder by polymorphisms in the MAOA, MAOB and COMT genes.
The monoamine oxidases (MAOA/B) and catechol-O-methyltransferase (COMT) enzymes break down regulatory components within serotonin and dopamine pathways, and polymorphisms within these genes are candidates for OCD susceptibility. Childhood trauma has been linked OCD psychopathology, but little attention has been paid to the interactions between genes and environment in OCD aetiology. This pilot study investigated gene-by-environment interactions between childhood trauma and polymorphisms in the MAOA, MAOB and COMT genes in OCD. Ten polymorphisms (MAOA: 3 variants, MAOB: 4 variants, COMT: 3 variants) were genotyped in a cohort of OCD patients and controls. Early-life trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Gene-by-gene (GxG) and gene-by-environment interactions (GxE) of the variants and childhood trauma were assessed using logistic regression models. Significant GxG interactions were found between rs362204 (COMT) and two independent polymorphisms in the MAOB gene (rs1799836 and rs6651806). Haplotype associations for OCD susceptibility were found for MAOB. Investigation of GxE interactions indicated that the sexual abuse sub-category was significantly associated with all three genes in haplotype x environment interaction analyses. Preliminary findings indicate that polymorphisms within the MAOB and COMT genes interact resulting in risk for OCD. Childhood trauma interacts with haplotypes in COMT, MAOA and MAOB, increasing risk for OCD.
Department of Psychiatry, Stellenbosch University, Tygerberg, South Africa; Department of Genetics, Stellenbosch University, Stellenbosch, South Africa. Electronic address: nwm@sun.ac.za.
N W
NW
McGregor
Department of Psychiatry, Stellenbosch University, Tygerberg, South Africa.
S M J
SMJ
Hemmings
The Hospital for Sick Children, Toronto, Ontario, Canada.
L
L
Erdman
Department of Psychiatry, Stellenbosch University, Tygerberg, South Africa.
I
I
Calmarza-Font
US/UCT MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
D J
DJ
Stein
US/UCT MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, Stellenbosch University, Tygerberg, South Africa.
C
C
Lochner
D000293:Adolescent; D000328:Adult; D000069586:Adult Survivors of Child Adverse Events; D000368:Aged; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics*; D009771:Obsessive-Compulsive Disorder / Q000235:genetics* / Q000523:psychology; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D055815:Young Adult
D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase
Catechol-O-methyltransferase (COMT); Gene-by-environment interaction (GxE); Genetics; Monoamine oxidase A (MAOA); Monoamine oxidase B (MAOB); Neuropsychiatry; Obsessive-compulsive disorder