TY - JOUR
T1 - No association between schizophrenia and polymorphisms in COMT in two large samples
AU - Williams, Hywel J.
AU - Glaser, Beate
AU - Williams, Nigel M.
AU - Norton, Nadine
AU - Zammit, Stanley
AU - Macgregor, Stuart
AU - Kirov, George K.
AU - Owen, Michael J.
AU - O'Donovan, Michael C.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/9
Y1 - 2005/9
N2 - 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.
AB - 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.
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U2 - 10.1176/appi.ajp.162.9.1736
DO - 10.1176/appi.ajp.162.9.1736
M3 - Review article
C2 - 16135635
AN - SCOPUS:24944500454
SN - 0002-953X
VL - 162
SP - 1736
EP - 1738
JO - American Journal of Psychiatry
JF - American Journal of Psychiatry
IS - 9
ER -