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Meta-analysis of association between the 5-HT2a receptor T102C polymorphism and schizophrenia.

Williams, Julie, McGuffin, Peter, Nothen, Markus and Owen, Michael John 1997. Meta-analysis of association between the 5-HT2a receptor T102C polymorphism and schizophrenia. The Lancet 349 (9060) , p. 1221. 10.1016/S0140-6736(05)62413-0

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Abstract

We have reported data from the European Multicentre Association Study of Schizophrenia (EMASS) which showed an association between schizophrenia and allele 2 (C) of the T102C polymorphism in exon 1 of the gene encoding the 5-hydroxytryptamine type 2a- (5-HT2a) receptor.1 The study involved 1210 individuals (571 patients and 639 ethnically matched controls) recruited from seven European countries, and replicated previous findings from a smaller Japanese sample.1 Further studies have been published2, 3, 4 and 5 most of which have been interpreted as offering little support for an association. However, our finding suggests that we have detected a small effect that might require a very large sample to replicate. Indeed, this was the reason why EMASS was established, to provide a large sample with adequate statistical power. We have done a meta-analysis of all published association studies between schizophrenia and the 5-HT2a T102C polymorphism. The meta-analysis included 15 studies (1533 patients and 1771 controls) of which seven made up the EMASS Collaboration. With the Woolf method1 of analysis we found a significant excess of allele 2 in patients (X 2-tests, p=0·0009, odds ratio=1·18, 95% CI=1·07-1·31) with no evidence of heterogeneity between studies (p=0·7 [the German EMASS sample and the Erdmann sample3 originate from the same population and were combined for this analysis]). A funnel plot of these studies (German groups combined) has an inverted funnel shape; it shows no evidence of a failure to publish small studies with low odds ratios, thus suggesting an absence of publication bias. We conclude that combining all available data gives increased evidence of an association between schizophrenia and allele 2 of the T102C 5-HT2a polymorphism. We have also detected a further polymorphism in an area of the gene, which may have functional significance, and seems to be in complete disequilibrium with T102C. This line of inquiry is being studied.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Elsevier
ISSN: 0140-6736
Last Modified: 04 Jun 2017 08:38
URI: http://orca.cf.ac.uk/id/eprint/81880

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