Meta-analysis shows association between the tryptophan hydroxylase (TPH) gene and schizophrenia

A number of studies have suggested an association between schizophrenia and the tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) genes. On the other hand, several studies attempting to replicate these findings have produced mixed results, possibly reflecting inadequate statistical power of the individual studies as well as the heterogeneity inherent in schizophrenia. In an attempt to clarify this inconsistency our meta-analysis has combined all the studies using multiple research methods published up to February 2006 to give a comprehensive picture of the role of three hydroxylase-related genes. The TPH A218C/A779C (OR = 1.18, 95% C.I. 1.06-1.33, P = 0.004) revealed a significant association with schizophrenia. However, the evidence for the TH and phenylalanine hydroxylase (PAH) genes was weak. No publication bias was detected in current studies. The findings, which may implicate the involvement of TPH in the pathogenesis of schizophrenia, have potentially important clinical, scientific and public health implications as well as providing a putative basis for the study of hydroxylase-related drugs. To our knowledge, this is the first meta-analysis of association between the three genes and schizophrenia.