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Genome-wide search for schizophrenia susceptibility loci: The NIMH genetics initiative and millennium consortium
Authors:C. Robert Cloninger  Charles A. Kaufmann  Stephen V. Faraone  Dolores Malaspina  Dragan M. Svrakic  Jill Harkavy-Friedman  Brian K. Suarez  Tara C. Matise  David Shore  Hang Lee  Carol L. Hampe  Debra Wynne  Caroline Drain  Paul D. Markel  Christopher T. Zambuto  Karin Schmitt  Ming T. Tsuang
Abstract:
Schizophrenia has a complex pattern of inheritance, indicative of interactions among multiple genes and environmental factors. The detection and replication of specific susceptibility loci for such complex disorders are facilitated by the availability of large samples of affected sib pairs and their nuclear families, along with standardized assessment and systematic ascertainment procedures. The NIMH Genetics Initiative 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 genome-wide scan to detect susceptibility loci for schizophrenia in 244 individuals from the nuclear families of 92 independent pairs of schizophrenic sibs ascertained by the NIMH Genetics Initiative. The 459 marker loci used in the scan were spaced at 10-cM intervals on average. Individuals of African descent were higher than those of European descent 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 frequencies of 73% of the marker loci differed significantly (P < .01) between individuals of European and African ancestry. However, regardless of ethnic background, this sample was largely comprised of schizophrenics with more than a decade of psychosis associated with pervasive social and occupational impairment. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:275–281, 1998. © 1998 Wiley-Liss, Inc.
Keywords:schizophrenia  genetics  linkage  family study
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