This collaborative proposal grows out of the investigators’ shared
interest in the genetic exploration of endophenotypes as a powerful
strategy for understanding
the genetics of schizophrenia. Over the past several years, the investigators
at the 7 Consortium sites have planned the proposed study. The 7 participating
sites are Harvard University, Mount Sinai School of Medicine, University of Colorado
Health Sciences Center, University of Pennsylvania, University of California,
Los Angeles, University of California, San Diego and University of Washington.
Each site has a successful record of peer-reviewed funding for family and genetic
studies of major neuropsychiatric disorders.
This proposal describes studies designed to measure 6 carefully selected endophenotypes
in schizophrenia patients and their relatives (see Response #3). Analyses will
determine whether these endophenotypes in schizophrenia patients and relatives
reflect the influence of a single common gene, or multiple genes. Specific statistical
strategies will then utilize these endophenotype measures in concert with a genome
scan in patients and family members, to identify genes regulating these 6 schizophrenia
endophenotypes. The remainder of this proposal describes the rationale for selecting
the 6 specific endophenotypes, and the strategies for their use in understanding
the genetics of schizophrenia.