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Identifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations

Molecular Psychiatry volume 10, pages 1037–1044 (2005)Cite this article

Abstract

The dystrobrevin-binding protein 1 (DTNBP1) gene on chromosome 6p has emerged as a potential susceptibility gene for schizophrenia. Although a number of attempts to replicate the original association finding have been successful, they have not identified any obvious pathogenic variants or a single at risk haplotype common to all populations studied. In the present study we attempted further replication in an independent sample of 638 nuclear families from the Han Chinese population of Sichuan Province, SW China. We also examined 580 Scottish schizophrenic cases and 620 controls. We genotyped 10 single-nucleotide polymorphisms (SNPs) in DTNBP1 that were used in the original report of association, plus rs2619538 (SNP ‘A’) in the putative promoter region, which has also been associated with schizophrenia. In the Chinese trios we found that two SNPs (P1635 and P1765) were significantly overtransmitted, but with alleles opposite to those reported in the original studies. SNPs P1757 and P1765 formed a common haplotype, which also showed significant overtransmission. In the Scottish cases and controls, no individual markers were significantly associated with schizophrenia. A single haplotype, which included rs2619538 and P1583, and one rare haplotype, composed of P1320 and P1757, were significantly associated with schizophrenia, but no previously reported haplotypes were associated. Based on the data from the Chinese population, our results provide statistical support for DTNBP1 as a susceptibility gene for schizophrenia, albeit with haplotypes different from those of the original study. However, our lack of replication in the Scottish samples also indicates that caution is warranted when evaluating the robustness of the evidence for DTNBP1 as genetic risk factor for schizophrenia.

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Acknowledgements

This work was partly funded by National Nature Science Foundation of China (TL), NARSAD (TL), Schizophrenia Research Fund (TL and DAC), the Psychiatry Research Trust (TL, RMM, DAC) and the Wellcome Trust for an International Collaborative award (TL, XS, DAC, XL). GSK also helped fund Scottish sample collection.

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Authors and Affiliations

  1. Department of Psychiatry, Psychiatry Laboratory, West China Hospital, Sichuan University, PR, China

    T Li, X Liu, X Sun, X Ma & Q Wang

  2. Division of Psychological Medicine, King's College London, Institute of Psychiatry, London, UK

    T Li, P C Sham, X Hu, R M Murray & D A Collier

  3. King's College London, Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK

    T Li, P C Sham & D A Collier

  4. Department of Mental Health, University of Aberdeen, Aberdeen, UK

    F Zhang, C Crombie, P Yates & D St Clair

  5. Department of Psychiatry, Chongqing Medical School, Chongqing, PR, China

    H Meng & W Deng

  6. Ravenscraig Hospital, Greenock, Scotland, UK

    N Walker

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  1. T Li
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  2. F Zhang
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  11. P Yates
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  14. R M Murray
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  16. D A Collier
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Correspondence to D A Collier.

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Li, T., Zhang, F., Liu, X. et al. Identifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations. Mol Psychiatry 10, 1037–1044 (2005). https://doi.org/10.1038/sj.mp.4001718

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  • DOI: https://doi.org/10.1038/sj.mp.4001718

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