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

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, Z(mp)=3.84 and empiric P=0.031 for delayed memory; Z=2.96, Z(mp)=3.4 and P=0.026 for verbal learning) and suggestive evidence for visual working memory on 2q36 (Z=2.80, Z(mp)=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.