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A haplotype within the DISC1 gene is associated with visual memory functions in families with a high density of schizophrenia

Molecular Psychiatry volume 10, pages 1097–1103 (2005)Cite this article

Abstract

We have previously reported evidence of linkage and association between markers on 1q42 and schizophrenia in a study sample of 498 multiply affected Finnish nuclear families, leading to the recent identification of four significantly associated haplotypes that specifically implicate the Translin-Associated Factor X (TRAX) and Disrupted in Schizophrenia 1 and 2 (DISC1 and DISC2) genes in the genetic etiology of schizophrenia. Previously, the DISC genes were found to be disrupted by a balanced translocation (1;11)(q42.1;q14.3) that cosegregated with schizophrenia and related disorders in a large Scottish pedigree. Interestingly, we also reported earlier suggestive linkage between endophenotypic quantitative traits of visual and verbal memory and microsatellite markers in close proximity to TRAX/DISC, on 1q41. Here, we tested if the identified allelic haplotypes of TRAX/DISC would be associated with visual and/or verbal memory function impairments that are known to aggregate with schizophrenia in families. One haplotype of DISC1, HEP3, displayed association with poorer performance on tests assessing short-term visual memory and attention. Analysis of affected and unaffected offspring separately revealed that both samples contribute to the observed association to visual working memory. These results provide genetic support to the view that the DISC1 gene contributes to sensitivity to schizophrenia and associated disturbances and affects short-term visual memory functions. This finding should stimulate studies aiming at the molecular characterization of how the specific alleles of DISC1 affect the visual memory functions and eventually participates in the development of schizophrenia.

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Acknowledgements

We acknowledge Ms OM Palo, Ms H Kilpinen, Ms J Meyer, and Mr A Parker for their contributing efforts in genotyping these samples, and doctors R Arajärvi, H Juvonen, M Muhonen, J Suokas, K Suominen, J Suvisaari, and J Hintikka for their diagnostic work. This work was partly funded by Wyeth Pharmaceuticals Inc., Millennium Pharmaceuticals Inc., Academy of Finland, Center of Excellence in Disease Genetics and research grant for LP, and Finnish Cultural Foundation, Paavo Koskinen and Aili and Paul Pennanen grants for WH. Mr Hennah is a member of the Helsinki Biomedical Graduate School and Dr Peltonen is the Gordon and Virginia MacDonald Distinguished Chair in Human Genetics at UCLA.

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Authors and Affiliations

  1. Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland

    W Hennah, T Paunio, J Ekelund, T Varilo & L Peltonen

  2. Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland

    A Tuulio-Henriksson, T Paunio, J Ekelund, T Partonen & J Lönnqvist

  3. Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland

    T Paunio & J Lönnqvist

  4. Department of Medical Genetics, University of Helsinki, Helsinki, Finland

    T Varilo & L Peltonen

  5. Departments of Psychology, Psychiatry and Biobehavioral Sciences, UCLA, CA, USA

    T D Cannon

  6. The David Geffen School of Medicine at UCLA, CA, USA

    L Peltonen

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  1. W Hennah
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Correspondence to L Peltonen.

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Hennah, W., Tuulio-Henriksson, A., Paunio, T. et al. A haplotype within the DISC1 gene is associated with visual memory functions in families with a high density of schizophrenia. Mol Psychiatry 10, 1097–1103 (2005). https://doi.org/10.1038/sj.mp.4001731

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