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Human Molecular Genetics Advance Access originally published online on June 15, 2004
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Human Molecular Genetics, 2004, Vol. 13, No. 16 1693-1702
DOI: 10.1093/hmg/ddh184
Human Molecular Genetics, Vol. 13, No. 16 © Oxford University Press 2004; all rights reserved

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 Paunio1,2,3,*, Annamari Tuulio-Henriksson2, Tero Hiekkalinna1, Markus Perola1, Teppo Varilo1, Timo Partonen2, Tyrone D. Cannon4,5,6, Jouko Lönnqvist2 and Leena Peltonen1,7,8

1Department of Molecular Medicine, 2Department of Mental Health and Alcohol Research, National Public Health Institute, 00300 Helsinki, Finland, 3Department of Psychiatry, Helsinki University Hospital, 00029 HUS, Helsinki, Finland, 4Department of Psychology, 5Department of Psychiatry and Biobehavioral Sciences, 6Department of Human Molecular Genetics, University of California, Los Angeles, CA 90095-1563, USA, 7Department of Medical Genetics, University of Helsinki, 00029 HUS, Helsinki, Finland and 8Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-7088, USA

Received February 27, 2004; Revised May 27, 2004; Accepted June 3, 2004

Research to identify predisposing genes for complex diseases relying solely on clinical diagnosis is probably not ideal. Here, we analyzed genome-wide 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 with diagnosis. We found evidence for a locus for verbal learning and memory on 4q21 (Z=3.01, Zmp=3.84 and empiric P=0.031 for delayed memory; Z=2.96, Zmp=3.4 and P=0.026 for verbal learning) and suggestive evidence for visual working memory on 2q36 (Z=2.80, Zmp=2.08 and P=0.093). 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 earlier mentioned regions, some evidence of linkage was observed for 2q, 6q, 7q, 11q, 13q, 14q, 18q and 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.

* To whom correspondence should be addressed at: Department of Molecular Medicine, National Public Health Institute, Biomedicum, PL 104, 00251 Helsinki, Finland. Tel: +358 947448751; Fax: +358 947448480; Email: tiina.paunio{at}ktl.fi


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