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

Abstract

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.