Research on the genetic epidemiology of schizophrenia is briefly and selectively reviewed. The following three salient features of schizophrenia that represent challenges to the design of linkage studies are identified: (1) The analysis of twin and family data has consistently failed to identify a single major gene effect upon schizophrenia risk; (2) the ascertainment of multiplex families does not guarantee the sampling of families who are segregating for the major gene even if a major gene effect exists; and (3) environmental influences appear to play an essential role in the etiology of at least some forms of schizophrenia. The implications of these features for the design of linkage studies in schizophrenia are discussed.
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