Paternal age and schizophrenia: a population based cohort study.

OBJECTIVE: To investigate the association of paternal age at conception with the risk of offspring developing schizophrenia. DESIGN: A population based cohort study. SETTING: Sweden. SUBJECTS: 754,330 people born in Sweden between 1973 and 1980 and still alive and resident in Sweden at age 16 years. MAIN OUTCOME MEASURES: Hospital admission with schizophrenia or non-schizophrenic, non-affective psychosis. RESULTS: After adjustment for birth related exposures, socioeconomic factors, family history of psychosis, and early parental death the overall hazard ratio for each 10 year increase in paternal age was 1.47 (95% confidence interval 1.23 to 1.76) for schizophrenia and 1.12 (0.98 to 1.29) for non-schizophrenic non-affective psychosis. This association between paternal age and schizophrenia was present in those with no family history of the disorder (hazard ratio for each 10 year increase in paternal age 1.60, 1.32 to 1.92), but not in those with a family history (0.91, 0.44 to 1.89) (P = 0.04 for interaction). CONCLUSIONS: Advancing paternal age is an important independent risk factor for schizophrenia. The stronger association between paternal age and schizophrenia in people without a family history provides further evidence that accumulation of de novo mutations in paternal sperm contributes to the overall risk of schizophrenia.