No association between schizophrenia and polymorphisms in COMT in two large samples

Hywel J. Williams, Beate Glaser, Nigel M. Williams, Nadine Norton, Stanley Zammit, Stuart Macgregor, George K. Kirov, Michael J. Owen, Michael C. O'Donovan

Research output: Contribution to journalReview articlepeer-review

70 Scopus citations


Objective: A valine/methionine polymorphism in the catechol O-methyltransferase (COMT) gene has been proposed to influence susceptibility to schizophrenia, as has a COMT haplotype in Ashkenazi Jewish and Irish subjects. The authors examined these hypotheses. Method: They reviewed data from more than 2,800 individuals, including almost 1,200 with schizophrenia, from case-control and family-based European association samples. Results: The authors found no support for the hypothesis that a valine/methionine polymorphism in the COMT gene influences susceptibility to schizophrenia or the hypothesis that a COMT haplotype influences susceptibility to schizophrenia in Ashkenazi Jewish and Irish subjects. Conclusions: The data suggest that the valine allele of COMT does not increase susceptibility to schizophrenia in Europeans and that the Ashkenazi or Irish haplotype does not increase susceptibility. Ethnic variation in the linkage disequilibrium structure at COMT means that the haplotype data may not generalize across populations. However, the authors' examination of the hypothesis that the valine allele confers susceptibility, with a particularly strong effect in Europeans, reveals that no such caveat applies.

Original languageEnglish (US)
Pages (from-to)1736-1738
Number of pages3
JournalAmerican Journal of Psychiatry
Issue number9
StatePublished - Sep 2005

ASJC Scopus subject areas

  • Psychiatry and Mental health


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