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

A meta-analysis of whole-genome linkage scans confirmed linkage between schizophrenia and markers on the long arm of chromosome 13. The gene HTR2A, which codes for the 5HT2a receptor, is located in this area. The T102C single nucleotide polymorphism of HTR2A has been the subject of much research. The production of the C-allele form of HTR2A is significantly less than that of the T-allele form in normal controls and schizophrenic patients. Although the association of schizophrenia with the C allele of HTR2A was confirmed by a meta-analysis 5 years ago, there was a continuous debate because negative findings were also considerable, which may have been due to ethnic differences in association. We performed another meta-analysis, since the number of available studies of this association has recently doubled. In the meta-analysis of 31 case-control association studies, we found a significant association between the C allele of the T102C polymorphism and schizophrenia, which was more pronounced in European samples than in the entire sample. We found significant heterogeneity in the allele-wise analysis (C vs. T) and homozygous genotype-wise analysis (CC vs. TT), both of which were at least partially explained by differences between samples from Asian and European countries. In East Asian countries, there was not a significant association with the C allele or CC homozygosity, indicating strong genetic differences and noncombinability of data between European and East Asian populations. Interestingly, the frequency of the T allele was much higher in East Asian patients and controls (59.5% and 57.5%, respectively) than in European patients and controls (40% and 43.5%, respectively). In five family-based association studies, we did not find significant evidence for association of the C allele with schizophrenia; yet, the pooled OR was 1.3 (95% CI=0.9-1.8, z=1.47, p=0.14), which is consistent with the results of the case-control studies. The effects of other genes, environmental effects on DNA methylation, or different methods of classification may be the causes for such heterogeneity, but more study in this area is needed.