Population impact of familial and environmental risk factors for schizophrenia: a nationwide study

Although several studies have examined the relative contributions of familial and environmental risk factors for schizophrenia, few have additionally examined the predictive power on the individual level and simultaneously examined the population impact associated with a wide range of familial and environmental risk factors. The authors present rate ratios (IRR), population-attributable risks (PAR) and sex-specific cumulative incidences of the following risk factors: parental history of mental illness, urban place of birth, advanced paternal age, parental loss and immigration status. We established a population-based cohort of 2,486,646million persons born in Denmark between 1 January 1955 and 31 December 1993 using Danish registers. We found that PAR associated with urban birth was 11.73%; PAR associated with one, respectively 2, parent(s) with schizophrenia was 2.67% and 0.12%. PAR associated with second-generation immigration was 0.70%. Highest cumulative incidence (CI=20.23%; 95% CI=18.10-22.62) was found in male offspring of 2 parents with schizophrenia. Cumulative incidences for male offspring or female offspring of a parent with schizophrenia were 9.53% (95% CI=7.71-11.79), and 4.89%, (95% CI 4.50-5.31). The study showed that risk factors with highest predictive power on the individual level have a relatively low population impact. The challenge in future studies with direct genetic data is to examine gene-environmental interactions that can move research beyond current approaches and seek to achieve higher predictive power on the individual level and higher population impact.