Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23

We have performed genetic linkage analysis in 13 large multiply affected fa milies, to test the hypothesis that there is extensive heterogeneity of lin kage for genetic subtypes of schizophrenia. Our strategy consisted of selec ting 13 kindreds containing multiple affected cases in three or more genera tions, an absence of bipolar affective disorder, and a single progenitor so urce of schizophrenia with unilineal transmission into the branch of the ki ndred sampled. DNA samples from these families were genotyped with 365 micr osatellite markers spaced at similar to 10-cM intervals across the whole ge nome. We observed LOD scores >3.0 at five distinct loci, either in the samp le as a whole or within single families, strongly suggesting etiological he terogeneity. Heterogeneity LOD scores >3.0 in the sample as a whole were fo und at 1q33.2 (LOD score 3.2; P = .0003), 5q33.2 (LOD score 3.6; P = .0001) , 8p22.1-22 (LOD score 3.6; P = .0001), and 11q21 (LOD score 3.1; P = .0004 ). LOD scores >3.0 within single pedigrees were found at 4q13-31 (LOD score 3.2; P = .0003) and at 11q23.3-24 (LOD score 3.2; P = .0003). A LOD score of 2.9 was also found at 20q12.1-11.23 within in a single family. The fact that other studies have also detected LOD scores >3.0 at 1q33.2, 5q33.2, 8p 21-22 and 11q21 suggests that these regions do indeed harbor schizophrenia- susceptibility loci. We believe that the weight of evidence for linkage to the chromosome 1q22, 5q33.2, and 8p21-22 loci is now sufficient to justify intensive investigation of these regions by methods based on linkage disequ ilibrium. Such studies will soon allow the identification of mutations havi ng a direct effect on susceptibility to schizophrenia.