GENOME-WIDE SEARCH FOR SCHIZOPHRENIA SUSCEPTIBILITY LOCI - THE NIMH-GENETICS-INITIATIVE AND MILLENNIUM-CONSORTIUM

Schizophrenia has a complex pattern of inheritance, indicative of inte ractions among multiple genes and environmental factors, The detection and replication of specific susceptibility loci for such complex diso rders are facilitated by the availability of large samples of affected sib pairs and their nuclear families, along with standardized assessm ent and systematic ascertainment procedures. The NIMH Genetics Initiat ive on Schizophrenia, a multisite collaborative study, was established as a national resource with a centralized clinical data base and cell repository. The Millennium Schizophrenia Consortium has completed a g enome-wide scan to detect susceptibility loci for schizophrenia in 244 individuals from the nuclear families of 92 independent pairs of schi zophrenic sibs ascertained by the NIMH Genetics Initiative. The 459 ma rker loci used in the scan were spaced at 10-cM intervals on average. Individuals of African descent were higher than those of European desc ent in their average heterozygosity (79% vs. 76%, P <.0001) and number of alleles per marker (9.2 vs. 8,4, P <.0001). Also, the allele frequ encies of 73% of the marker loci differed significantly (P <.01) betwe en individuals of European and African ancestry. However, regardless o f ethnic background, this sample was largely comprised of schizophreni cs with more than a decade of psychosis associated with pervasive soci al and occupational impairment. Am. J, Med, Genet, (Neuropsychiatr, Ge net,) 81:275-281, 1998, (C) 1998 Wiley-Liss, Inc.