The relative importance of genetics and the environment in causing schizophrenia is still being debated. Although the high proportion of monozygote cotwins of schizophrenia patients who are discordant suggests that there may be a significant environmental contribution to the development of schizophrenia, this discordance is predicted by an accumulative multimutation model of schizophrenia onset constructed here implying a genetic origin of schizophrenia. In this model, schizophrenics are viewed as having been born with the genetic susceptibility to develop schizophrenia. As susceptible gene carriers age, they randomly accumulate the necessary mutations to cause schizophrenia, the last needed mutation coinciding with disease onset. The mutation model predicts that the concordance rate in monozygote twin studies will monotonically increase with age, theoretically approaching 100% given sufficient longevity. In dizygote cotwins of schizophrenia patients, the model predicts that at least 71% of cotwins are incapable of developing schizophrenia even though every cotwin and their schizophrenic twin shared a similar early environment. The multimutation model is shown to fit all of the monozygote and dizygote concordance rate data of the principle classical twin studies completed before 1970 considered in this paper. Thus, the genetic hypothesis of schizophrenia can be tested by bringing these studies up to date. 1. Introduction Schizophrenia is a brain disease characterized by delusions, hallucinations, and behavioral and functional disturbances. Once the disease develops, most patients’ functioning is seriously impaired. Discovering its cause and cure remain some of the biggest challenges to modern medicine and neuroscience. A fundamental debate on the etiology of schizophrenia is the relative importance of genetics and environmental factors in causing the disease. A consistently higher concordance rate of schizophrenia in monozygotic twins than in dizygotic twins supports the genetic hypothesis. By contrast, external environmental factors are thought to contribute to the development of schizophrenia because a significant proportion of monozygotic twins are discordant. However, this inference from this fact is challenged by the mutation model to be developed in this paper. The high rate of discordance in monozygotic twins (around 50%) is typically credited to environmental factors [1–3]. However, there is also strong evidence to counter this explanation of this discordance. In monozygote twin studies, the risk for schizophrenia in the offspring of the
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