1. ¹Cancer Research UK GPRG, Department of Clinical Pharmacology, University of Oxford, Oxford, UK
2. ²Cancer Research UK Centre for Statistics in Medicine, University of Oxford, Oxford, UK
3. ³Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

Correspondence: Dr MR Munafò, PhD, Cancer Research UK GPRG, Department of Clinical Pharmacology, University of Oxford, Oxford OX2 6HE, UK. E-mail: marcus.munafo@clinpharm.ox.ac.uk

Received 29 November 2004; Revised 31 January 2005; Accepted 14 February 2005; Published online 12 April 2005.

Abstract

There is strong evidence for a genetic contribution to schizophrenia, but the contribution of individual candidate genes remains uncertain. We attempted to replicate a recent meta-analysis that reported an association of the catechol O-methyltransferase (COMT) Val allele with schizophrenia, and suggested that this effect may be moderated by ancestry. We included reports published subsequent to the original meta-analysis, and included a formal test of the moderating effect of ancestry in order to test whether the association operates differently in populations of European ancestry compared to populations of Asian ancestry. A corrected P-value for the 5% significance threshold was employed where appropriate, using Bonferroni's method, and studies that demonstrated departure from Hardy–Weinberg equilibrium among controls were excluded. When all studies were included in a meta-regression, there was evidence for a significant association of COMT Val allele frequency with schizophrenia case status and a significant main effect of ancestry. The interaction of COMT Val allele frequency and ancestry was also significant. However, when only studies that reported allele frequencies that did not depart significantly from Hardy–Weinberg equilibrium among controls were included, these effects were no longer significant. The results of our meta-analysis do not support an association between the COMT Val allele and schizophrenia case status, and do not support recent claims that this association may be moderated by ancestry.