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The trace amine receptor 4 gene is not associated with schizophrenia in a sample linked to chromosome 6q23

Molecular Psychiatry volume 11, pages 119–121 (2006)Cite this article

Trace amine receptors are plausible candidate genes for schizophrenia given the role of biogenic amines in this disorder and the fact that these receptors are activated by endogenous amines with amphetamine-like activity.1, 2 The trace amine receptor 4 gene (TRAR4, chromosome 6q23.2) is also an important positional candidate. Since the initial report of Cao et al.,3 several studies have reported linkage of schizophrenia to chromosome 6q. Recently, Duan et al.4 reported association of a single SNP in TRAR4 and two SNPs in perfect linkage disequilibrium with it, with schizophrenia, in families that previously showed linkage to 6q13–q26. Association with schizophrenia was not replicated in case–control samples of Japanese5 or Chinese6 origin, but was observed with bipolar disorder in German family-based and case–control samples,7 all without prior evidence for linkage to chromosome 6q.

Based on an autosomal scan of 21 Arab Israeli families, we reported linkage of schizophrenia to chromosome 6q23 that was significant at a genome-wide level with a nonparametric LOD score (NPL) of 4.60 (P=0.000004) at 136.3 Mb.8 Fine mapping led to an increase of the NPL to 4.98 (P=0.00000058)9 and reduced the putative susceptibility region (NPL-1) to 3.90 Mb. Therefore, it was highly pertinent to determine whether association with TRAR4 could be replicated in our sample.

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References

  1. Premont RT, Gainetdinov RR, Caron MG . Proc Natl Acad Sci USA 2001; 98: 9474–9475.

  2. Branchek TA, Blackburn TP . Curr Opin Pharmacol 2003; 3: 90–97.

  3. Cao Q et al. Genomics 1997; 43: 1–8.

  4. Duan J et al. Am J Hum Genet 2004; 75: 624–638.

  5. Ikeda M et al. Schizophr Res 2005 (doi:10.1016/j.schres.2005.05.002).

  6. Duan S et al. J Neural Transm 2005, Aug 3 (Epub ahead of print).

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  9. Levi A et al. Eur J Hum Genet 2005; 13: 763–771.

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Acknowledgements

This work was supported in part by grants from the Israel Ministry of Science (Korean–Israeli Human Genome Collaboration) and the Benoziyo Center for Neurological Disease.

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Authors and Affiliations

  1. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel

    D Amann, N Avidan, E Ben-Asher, J S Beckmann & D Lancet

  2. Department of Psychiatry, Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    K Kanyas, Y Kohn & B Lerer

  3. Regional Mental Health Center, Taibe, Israel

    A Hamdan

  4. Biostatistics Unit, Center for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada

    F Macciardi

  5. Dépt de Génétique Médicale, CHUV-UNIL, Lausanne, Switzerland

    J S Beckmann

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  1. D Amann
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  2. N Avidan
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  4. Y Kohn
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  9. D Lancet
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  10. B Lerer
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Correspondence to B Lerer.

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Amann, D., Avidan, N., Kanyas, K. et al. The trace amine receptor 4 gene is not associated with schizophrenia in a sample linked to chromosome 6q23. Mol Psychiatry 11, 119–121 (2006). https://doi.org/10.1038/sj.mp.4001752

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