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

• Published in: The Lancet (British edition) 1996-05, Vol.347 (9011), p.1294-1296
• Main Authors: European Multicentre Association Study of Schizophrenia (EMASS) Group, Williams, J., Spurlock, G., McGuffin, P., Owen, M.J., Mallet, J., Nöthen, M.M., Gill, M., Aschauer, H., Nylander, P-O., Macciardi, F.
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Biological and medical sciences; Genetics; Genotypes; Heterogeneity; Lymphocytes; Medical sciences; Mental disorders; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Schizophrenia
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(96)90939-3

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.