Schizophrenia: A genome scan targets chromosomes 3p and 8p as potential sites of susceptibility genes

Using a systematically ascertained sample of 57 families, each having 2 or more members with a consensus diagnosis of schizophrenia (DSM-III-R criteria), we have carried out linkage studies of 520 loci, covering approximately 70% of the genome for susceptibility loci for schizophrenia. A two-stage strategy based on lod score thresholds from simulation studies of our sample identified regions for further exploration. In each region, a dense map of highly informative dinucleotide repeat polymorphisms (heterozygosity greater than .70) was analyzed using dominant, recessive, and 'affected only' models and nonparametric sib pair identity-by-descent methods. For one region, 8p22-p21, affected sib-pair analyses gave a P value = .0001, corresponding to a lod score approximately equal to 3.00. For 8p22- p21, the maximum two-point lod score occurred using the 'affected only' recessive model (Z(MAX) = 2.35; θ(M) = θ(F)); allowing for a constant sex difference in recombination fractions found in reference pedigrees, Z(MAX) = 2.78 (θ(M)/θ(F) = 3). For a second region, 3p26-p24, the maximum two-point lod score was 2.34 ('affected only' dominant model), and the affected sib- pair P value was .01. These two regions are worthy of further exploration as potential sites of susceptibility genes for schizophrenia.