AN INTERNATIONAL 2-STAGE GENOME-WIDE SEARCH FOR SCHIZOPHRENIA SUSCEPTIBILITY GENES

Schizophrenia is thought to be a multifactorial disease with complex m ode of inheritance (1,2). Using a two-stage strategy for another compl ex disorder, a number of putative IDDM-susceptibility genes have recen tly been mapped(3). We now report the results of a two-stage genome-wi de search for genes conferring susceptibility to schizophrenia. In sta ge I, model-free linkage analyses of large pedigrees from Iceland, a g eographical isolate, revealed 26 loci suggestive of linkage. In stage II, ten of these were followed-up in a second international collaborat ive study comprising families from Austria, Canada, Germany, Italy, Sc otland, Sweden, Taiwan and the United States. Potential linkage findin gs of stage I on chromosomes 6p, 9 and 20 were observed again in the s econd sample. Furthermore, in a third sample from China, fine mapping of the 6p region by association studies also showed evidence for linka ge or linkage disequilibrium. Combining our results with other recent findings(4,5) revealed significant evidence for linkage to an area dis tal of the HLA region on chromosome 6p. However, in a fourth sample fr om Europe, the 6p fine mapping finding observed in the Chinese sample could not be replicated. Finally evidence suggestive of locus heteroge neity and oligogenic transmission in schizophrenia was obtained.