Initial genome-wide scan for linkage with schizophrenia in the Japanese Schizophrenia Sib-pair Linkage Group (JSSLG) families

To determine if there are common genes that contribute to the susceptibility for schizophrenia, first-stage genome-wide scan was carried out by genotyping 417 short-tandem repeat (STR) markers in 338 individuals from 130 families with 148 affected sib-pairs identified at 16 sites nationwide in Japan. Data was from the Japanese Schizophrenia Sib-pair Linkage Group (JSSLG), which is a multi-site collaborative study group established to create a national resource for genetic studies of schizophrenia in Japan. All subjects were Japanese, and the probands and their siblings had schizophrenia. Multipoint non-parametric linkage analysis and exclusion mapping were performed with GENEHUNTER software. Simulation studies suggested that in the absence of linkage we could expect one multipoint maximum LOD score (MLS) of 1.9 per genome scan. An MLS of 3.7 would be expected only once in every 20 genome scans and thus corresponds to a genome-wide significance of 0.05. No loci in the initial screen fulfilled the criteria for significant or suggestive evidence for linkage. Ten chromosomes (1, 2, 3, 4, 5, 8, 9, 14, 17, and 20) had at least one region with a nominal P value < 0.05. Susceptibility genes with λs of 3 and 2 were excluded from 98 and 70% of the genome, respectively. Our results suggest that common genes that contribute significantly to susceptibility for schizophrenia are unlikely to exist in the Japanese population.