1. ¹Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
2. ²Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland
3. ³Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland
4. ⁴Department of Medical Genetics, University of Helsinki, Helsinki, Finland
5. ⁵Departments of Psychology, Psychiatry and Biobehavioral Sciences, UCLA, CA, USA
6. ⁶The David Geffen School of Medicine at UCLA, CA, USA

Correspondence: Dr L Peltonen, Department of Medical Genetics, University of Helsinki, Biomedicum/KTL, MLO, PL 104, 00251, Helsinki, Finland. E-mail: Leena.Peltonen@ktl.fi

Received 25 March 2005; Revised 6 July 2005; Accepted 19 July 2005; Published online 16 August 2005.

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.