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Human Molecular Genetics Advance Access published online on June 15, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh184
© 2004 by Oxford University Press
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Article

Search for cognitive trait components of schizophrenia reveals a locus for verbal learning and memory on 4q and for visual working memory on 2q

Tiina Paunio 1*, Annamari Tuulio-Henriksson 2, Tero Hiekkalinna 3, Markus Perola 3, Teppo Varilo 3, Timo Partonen 2, Tyrone D. Cannon 4, Jouko Lönnqvist 2, Leena Peltonen 5

1 Department of Molecular Medicine, National Public Health Institute, Biomedicum, PL 104, 00251 Helsinki, Finland; Department of Mental Health and Alcohol Research, National Public Health Institute, 00290 Helsinki, Finland; Department of Psychiatry, Helsinki University Hospital, 00029 HUS, Helsinki, Finland
2 Department of Mental Health and Alcohol Research, National Public Health Institute, 00290 Helsinki, Finland
3 Department of Molecular Medicine, National Public Health Institute, 00290 Helsinki, Finland
4 Departments of Psychology, Psychiatry and Biobehavioral Sciences, and Human Molecular Genetics, University of California, Los Angeles, California 90095-1563, USA
5 Department of Molecular Medicine, National Public Health Institute, 00290 Helsinki, Finland; Department of Medical Genetics, University of Helsinki, 00029 HUS, Helsinki, Finland; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California 90095-7088, USA

* To whom correspondence should be addressed. E-mail: tiina.paunio{at}ktl.fi.


  Abstract

Research to identify predisposing genes for complex diseases relying solely on clinical diagnosis is probably not ideal. Here, we analysed genomewide data for 168 schizophrenia families using neuropsychological variables associated with disease susceptibility, with the aid of SOLAR, a program for variance component analysis. The linkage signal was greatly accentuated by application of the quantitative traits compared to diagnosis. We found evidence for a locus for verbal learning and memory on 4q21 (Z = 3.01, Zmp = 3.84 and empiric P = .031 for delayed memory; Z = 2.96, Zmp = 3.4 and P = .026 for verbal learning) and suggestive evidence for visual working memory on 2q36 (Z = 2.80, Zmp = 2.08 and P = .093). In addition, some evidence emerged for a locus for recognition memory on 10p13, visual attention on 15q22, and executive function on 9p22 in the complete sample, as well as for delayed memory on 8q12, semantic clustering and intrusions on 1q42, and visual attention on 3p25 in the genealogically distinctive sample subsets. Of the loci linked to schizophrenia in diverse populations, in addition to the above-mentioned regions, some evidence of linkage was observed to 2q, 6q, 7q, 11q, 13q, 14q, 18q and to 22q. Our results reveal initial information on the effect of the loci associated with schizophrenia in multiple studies, and emphasize the value of trait components in the search for susceptibility loci for complex diseases.


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