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The met158 allele of catechol-O-methyltransferase (COMT) is associated with obsessive-compulsive disorder in men: case–control study and meta-analysis

Abstract

Existing data suggest a genetic association between the met158 allele of catechol-O-methyltransferase (COMT) and obsessive-compulsive disorder (OCD). However, the results are inconclusive and complicated by possible gender differences. We sought to resolve the question in two ways. First, we carried out a new case–control study in 87 adults with OCD and 327 healthy comparison subjects. The study replicated reports of an increased met158 allele frequency in men with OCD (odds ratio (OR)=1.91, 95% confidence interval (CI) 1.07–3.40, P=0.026), with no effect in women (OR=1.13, 95% CI 0.74–1.72, P=0.56). Second, we performed a meta-analysis of all published case–control data (n=1908 subjects). This revealed an association of COMT met158 with OCD (OR=1.23, 95% CI 1.06–1.42, P=0.005) and an interaction with gender (z=4.27, P<0.0001). The association between COMT met158 and OCD was present in men (OR=1.88, 95% CI 1.45–2.44, P<0.001) but not in women (OR=0.98, 95% CI 0.78–1.22, P=0.83). We conclude that COMT may play a role in the genetic aetiology of OCD in men. The biological plausibility of the association is increased by the functionality of the val158met polymorphism in terms of its effect on COMT enzyme activity, and by the role of COMT in cortical dopamine signalling and information processing. The finding also extends the evidence for sexual dimorphism in COMT and in OCD.

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Acknowledgements

ECP was recipient of a Medical Research Council (MRC) studentship. PJH is a co-PI of the MRC Neurobiology of Mood Disorders Co-Operative Group, which provided additional support. We thank Ann Roberts and Annabel Banks for help with recruitment and clinical assessments, Phil Burnet and Khatija Parekh for technical assistance, John Geddes for the meta-regression, and Jonathan Flint, Christine Lochner, Marcus Munafo and Liz Tunbridge for advice and discussion.

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Correspondence to P J Harrison.

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Pooley, E., Fineberg, N. & Harrison, P. The met158 allele of catechol-O-methyltransferase (COMT) is associated with obsessive-compulsive disorder in men: case–control study and meta-analysis. Mol Psychiatry 12, 556–561 (2007). https://doi.org/10.1038/sj.mp.4001951

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