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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Association of a haplotype in the serotonin 5-HT4 receptor gene (HTR4) with Japanese schizophrenia.

The serotonin 5-HT(4) receptor (5-HT(4)) is implicated in cognitive function, of which impairment is hypothesized as one of the core disturbances of schizophrenia. Linkage analysis shows that 5q33.2, in which HTR4 is located, is schizophrenia-susceptibility loci. We therefore hypothesized that variation in the 5-HT(4) receptor gene (HTR4) modifies genetic susceptibility to schizophrenia. HTR4 coding regions and introns that include the branch sites of HTR4 were investigated in 96 unrelated Japanese schizophrenics using denaturing high-performance liquid chromatography analysis. One silent single nucleotide polymorphism (SNP) within the coding region and six intronic SNPs were detected. 353 + 6G > A was located in the branch site that could be effect to RNA splicing. None of the four SNPs, in which rare-allele frequencies were more than 10% was associated with 189 schizophrenics, in comparison to 299 controls. However, a highly significant association between schizophrenia and haplotype A-T (OR = 0.13 [0.03-0.58]) was detected. These findings suggest that haplotype A-T itself may inhibit the occurrence of schizophrenia, or that another susceptible genetic variants may exist within linkage disequilibrium.[1]


  1. Association of a haplotype in the serotonin 5-HT4 receptor gene (HTR4) with Japanese schizophrenia. Suzuki, T., Iwata, N., Kitamura, Y., Kitajima, T., Yamanouchi, Y., Ikeda, M., Nishiyama, T., Kamatani, N., Ozaki, N. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2003) [Pubmed]
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