Schizophrenia: A genome search targets chromosomes 3 and 8 for exploration

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 searched approximately 75% of the genome for susceptibility loci for schizophrenia. Genetic linkage studies of 520 loci have been performed using a complex autosomal dominant model incorporating age-at-onset and certainty of the diagnosis. Results were analyzed under the hypothesis of heterogeneity using the A-test and the Liang test. A two-stage strategy based on lod score thresholds from simulation studies of our sample identified regions for further exploration (hot spots). In each region, a dense map of highly informative dinucleotide repeat polymorphisms (heterozygosity greater than .70) is analyzed using linkage studies with dominant, recessive, and affected only models and non-parametric sib pair identity-by-descent methods (SIBPAL, S.A.G.E. 2.1). In no region has a lod score > 3 been observed; however, affected sib pair analyses gave a p-value of .0001 corresponding to a lod score > 3. Current {open_quote}hot spots{close_quote} on chromosomes 3p26-p24 and 8p22-p21 will be presented. For 3p26-p24, the maximum two-point lod score is 1.97 (dominant model) and the SIBPAL p-value is .02. For 8p22-p21, the maximum two-point lod score is 2.02 (recessive model) and the SIBPALmore » p-value is .0001.« less