Although there is convincing evidence for the presence of both environmental and genetic risk factors for schizophrenia, pinpointing these risk factors has been difficult. We will investigate cytomegalovirus (CMV) as a risk factor for schizophrenia in conjunction with polymorphisms in six positional candidate genes: TNF, LTA, MICB, IL-1beta, IL1RN, and IL-10. We will conduct a systematic, stepwise evaluation of these genes in multiple case/control and family-based samples. Evaluation of environmental and genetic main effects will first be evaluated in parallel using two case/control samples. Gene-environment correlation will be calculated from both control samples, and then gene-environment interaction effects will be investigated in schizophrenia cases. Family-based samples from multiple populations will be used to test the validity and generalizability of our findings. In addition, family-based studies will allow additional forms of exploratory analyses, such as examining parent-specific transmission of an allele, or associations among the mothers of probands. Identification of an interaction between CMV and genetic polymorphisms could hold one of the keys to the molecular etiology of schizophrenia and lead to new methods for diagnosis, therapy and prevention. [unreadable] [unreadable]