Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene. European Multicentre Association Study of Schizophrenia (EMASS) Group.
BACKGROUND
An association between schizophrenia and the T102C polymorphism of the gene for 5-hydroxytryptamine type 2a (5-HT2a) receptor has been reported; the proportion of allele 2 of this polymorphism is higher than expected among schizophrenic patients. We looked for an association between schizophrenia and this variant of the 5-HT2a-receptor gene in a large multicentre study.


METHODS
Seven countries recruited 1210 participants: 571 white schizophrenic patients and 639 ethnically matched controls. All patients had a diagnosis of schizophrenia or schizoaffective disorder. High-molecular-weight DNA was isolated from lymphocytes. PCR amplification and restriction enzyme digestion was used to examine sequence variation of the 5-HT2a-receptor gene. Genotypes 1/1, 1/2, and 2/2 were assigned. Woolf's method was used to look for an association between schizophrenia and allele 2 and the 2/2 genotype.


RESULTS
We found a significant overall association between schizophrenia and allele 2 with an odds ratio of 1.3 (95% Cl 1.1-1.53, p = 0.003). No evidence for heterogeneity was observed between samples. We found a highly significant excess of the 1-2/2-2 genotypes in schizophrenia (p = 0.008) with a relative risk of 1.7 (1.22-2.36) and an attributable fraction of 0.35.


CONCLUSIONS
Our findings suggest that the gene for 5-HT2a-receptor, or a locus in linkage disequilibrium with it, confers susceptibility to schizophrenia. Allele 2 is common in the population and it is, therefore, likely that this variant, or a nearby polymorphism, may affect a significant proportion of schizophrenic patients.
Williams
J
J
Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK.
Spurlock
G
G
McGuffin
P
P
Mallet
J
J
Nöthen
M M
MM
Gill
M
M
Aschauer
H
H
Nylander
P O
PO
Macciardi
F
F
Owen
M J
MJ
D000483:Alleles; D005060:Europe; D005838:Genotype; D006801:Humans; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin