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Updated: Jul 11, 2026

A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
The tryptophan hydroxylase 1 (TPH1) gene and risk of schizophrenia: a moderate-scale case-control study and
Yuichiro Watanabe1, Ayako Nunokawa, Naoshi Kaneko
1Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, 757 Asahimachidori-ichibancho, Niigata 951-8510, Japan. yuichiro@med.niigata-u.ac.jp
Abstract:
Serotonin (5-hydroxytryptamine [5-HT]) may be implicated in both the pathophysiology of schizophrenia and in mediating atypical antipsychotic drug effects. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme involved in the synthesis of 5-HT. Some genetic variants of the TPH1 gene have been tested for their associations with schizophrenia, but with conflicting results. To assess whether TPH1 is implicated in vulnerability to schizophrenia, we conducted a case-control association study (409 patients and 440 controls) for six single nucleotide polymorphisms in Japanese subjects and performed an updated meta-analysis. There were no significant associations between the polymorphisms or haplotypes of TPH1 and schizophrenia in our Japanese subjects. Our updated meta-analysis, which included six population-based case-control studies, suggests the possible involvement of the TPH1 218A allele in susceptibility to schizophrenia. To draw any conclusion, however, further studies using larger sample sizes should be carried out in various ethnic populations.
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