Schizophrenia spectrum disorders: an autosomal-wide scan in multiplex pedigrees

Genome-wide linkage studies, examining the relationship between the schizop hrenia syndrome(s) and possible susceptibility regions within the human gen ome have identified multiple regions within which linkage to the syndrome m ay be explored. No regions have been found to provide supportive evidence f or linkage in all cohorts. These findings are consistent with the schizophr enia syndrome being genetically heterogeneous, with genetic susceptibility arising from multiple sites which are differentially distributed in from pe digree to pedigree. The authors present data from an autosomal-wide scan of 30 multiplex pedigrees, each with a mean of 4.1 members affected with a sc hizophrenia spectrum disorder with respect to regions of interest for linka ge with the schizophrenia spectrum disease(s). Partial, though not signific ant replications of susceptibility sites at D1S518 (P = 0.029) described by Shaw et al. (1998: Shaw, S.H., Kelly, M., Smith, A.B., Shields, G., Hopkin s, P.J. Loftus, J., Laval, SM., Vita, A., DeHert, M., Cardon, L.R., Crow, T .J., Sherrington, R., DeLisi, L.E., 1998. A Genome-wide search for schizoph renia susceptibility genes. Am. J. Med. Genet. (Neuropsychiatric Genet.) 81 , 364-376.), and at D5S426 (P = 0.015) described by Silverman et al. (1996: Silverman, J.M., Greenberg, D.A., Altstiel, L.D., Siever, L.J., Mohs, R.C. . Smith, C.J., Zhou, G., Hollander, T.Y., Yang, X.-P., Kedache, M., Li, G., Zaccario, M.L., Davis, K,L., 1996. Evidence of a locus for schizophrenia a nd related disorders on the short arm of chromosome 5 in a large pedigree. Am. J. Med. Genet. 67, 162-171.) were documented using multipoint non-param etric (NPL) statistics. Two additional novel regions worthy of further inve stigation were identified at D1S1150 (P = 0.004) and at D20S171 (P = 0.009) . Previously reported genomic regions of interest for the schizophrenias ar e reviewed in the context of the same/flanking markers utilized with the pr esent cohort of pedigrees. The data further suggests that only a fraction o f pedigrees multiplex for schizophrenia link at any single susceptibility r egion. (C) 2001 Elsevier Science B.V. All rights reserved.