Linkage of familial schizophrenia to chromosome 13q32

Abstract

Over the past 4 years, a number of investigators have reported findings suggestive of linkage to schizophrenia, with markers on chromosomes 13q32 and 8p21, with one recent study by Blouin et al. reporting significant linkage to these regions. As part of an ongoing genome scan, we evaluated microsatellite markers spanning chromosomes 8 and 13, for linkage to schizophrenia, in 21 extended Canadian families. Families were analyzed under autosomal dominant and recessive models, with broad and narrow definitions of schizophrenia. All models produced positive LOD scores with markers on 13q, with higher scores under the recessive models. The maximum three-point LOD scores were obtained under the recessive-broad model: 3.92 at recombination fraction (theta).1 with D13S793, under homogeneity, and 4.42 with alpha=.65 and straight theta=0 with D13S793, under heterogeneity. Positive LOD scores were also obtained, under all models, for markers on 8p. Although a maximum two-point LOD score of 3.49 was obtained under the dominant-narrow model with D8S136 at straight theta=0.1, multipoint analysis with closely flanking markers reduced the maximum LOD score in this region to 2. 13. These results provide independent significant evidence of linkage of a schizophrenia-susceptibility locus to markers on 13q32 and support the presence of a second susceptibility locus on 8p21.

Figure 1

Three-point analysis of schizophrenia, with D13S793, and D13S779 under the recessive-broad genetic model, under homogeneity and heterogeneity. D13S793 is at map position 0. α=.65 for the heterogeneity LOD score.

Figure 2

Four-point analysis of schizophrenia, with D8S560, D8S136, and D8S298, under homogeneity and the dominant-narrow and recessive-narrow genetic models. D8S560 is at map position 0. Because of their close proximity, the positions of the three markers are indicated by a single point, on the X-axis, that spans map position 0–0.5 cM. Also because of proximity, the plotted points for D8S136 and D8S298 overlap and appear as a single point on the LOD-score plot.