Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene

Summary Background An association between schizophrenia and the T102C polymorphism of the gene for 5-hydroxytryptamine type 2a (5-HT 2a) 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-HT 2a-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-HT 2a-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 2/2genotype. Findings 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 1-2/2-2genotypes in schizophrenia (p=0·008) with a relative risk of 1·7 (1·22-2·36) and an attributable fraction of 0·35. Interpretation Our findings suggest that the gene for 5-HT 2a-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.