Family history, place and season of birth as risk factors for schizophrenia in Denmark: A replication and reanalysis

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Abstract
Background: Although a family history of schizophrenia is the strongest individual risk factor for schizophrenia, environmental factors related to urbanicity may contribute to a substantial proportion of the population occurrence of the disease.Aims: This study replicates previous findings in four mutually exclusive Danish study populations, including out-patient information, ICD–10 diagnoses of schizophrenia, and a broader adjustment for mental illness in family members.Method: We established a population-based cohort of 2.66 million Danish people using data from the Civil Registration System linked with the Psychiatric Case Register.Results: Overall, 10 264 persons developed schizophrenia during the 50.7 million person-years of follow-up. The risk of schizophrenia was increased by urbanicity of place of birth and by family history of schizophrenia or other mental disorders.Conclusions: Urban–rural differences of schizophrenia risk were replicated and could not be associated with the potential sources of bias we assessed. Environmental factors underlying the effect of place of birth are major determinants of schizophrenia occurrence at the population level, although the effect of family history is the strongest at the individual level.