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.


METHODS
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.
Williams
Hywel J
HJ
Department of Psychological Medicine, Henry Wellcome Building for Biomedical Research, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.
Glaser
Beate
B
Williams
Nigel M
NM
Norton
Nadine
N
Zammit
Stanley
S
MacGregor
Stuart
S
Kirov
George K
GK
Owen
Michael J
MJ
O'Donovan
Michael C
MC
D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D007585:Jews / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D008715:Methionine / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D014633:Valine / Q000235:genetics; D044465:White People / Q000235:genetics
D005819:Genetic Markers; D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine