No Association Between Schizophrenia and Polymorphisms in COMT in Two Large Samples

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...

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Bibliographic Details
Published in:The American journal of psychiatry 2005-09, Vol.162 (9), p.1736-1738
Main Authors: Williams, Hywel J., Glaser, Beate, Williams, Nigel M., Norton, Nadine, Zammit, Stanley, Macgregor, Stuart, Kirov, George K., Owen, Michael J., O'Donovan, Michael C.
Format: Article
Language:English
Subjects:
Adult and adolescent clinical studies
Biological and medical sciences
Brain
Case-Control Studies
Catechol O-Methyltransferase - genetics
Female
Genes
Genetic Markers
Genetic Predisposition to Disease
Genotype
Haplotypes - genetics
Humans
Ireland - epidemiology
Jews - genetics
Linkage Disequilibrium
Male
Medical sciences
Methionine - genetics
Polymorphism
Polymorphism, Genetic
Polymorphism, Single Nucleotide - genetics
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Psychoses
Schizophrenia
Schizophrenia - enzymology
Schizophrenia - epidemiology
Schizophrenia - genetics
Valine - genetics
Whites - genetics
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Summary: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.
ISSN:0002-953X
1535-7228
DOI:10.1176/appi.ajp.162.9.1736