Linkage studies of schizophrenia are hampered by low recurrence risk and a non-Mendelian mode of transmission. Although schizophrenia itself is not highly penetrant, traits that are associated with schizophrenia and that occur at a higher rate in relatives of schizophrenics could serve as useful pointers to the gene(s) for schizophrenia in linkage analysis. Prominent among these associated traits are eye tracking dysfunction, thought disorder, craniofacial dysmorphology, and clinical signs and symptoms associated with the schizophrenia spectrum. The investigators propose to maximize discrimination among genotypes by mapping these more prevalent associated quantitative traits, rather than relying on an all-or-none disease phenotype. Because this strategy bases affectedness on traits that have a higher genetic signal than schizophrenia, the investigators expect that it will increase the power of linkage analysis. The investigators will use both nonparametric and model-dependent methods to test for linkage in a sample comprising 160-208 sibling pair combinations. They will include recent modifications of the Haseman-Elston method as well as lod score analysis. They will use discriminant functions as quantitative phenotypes. They will scan the entire genome for evidence of linkage to individual quantitative phenotypes and combinations of quantitative phenotypes by typing highly informative multi-allele markers, using a map of 10 cM or less. Robust statistical methods for evaluating the results of genomic scans will be developed.
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