Association between paternal age and risk of schizophrenia: a nationwide population-based study

J Assist Reprod Genet. 2021 Jan;38(1):85-93. doi: 10.1007/s10815-020-01936-x. Epub 2020 Aug 30.


Purpose: To study the association between paternal age and schizophrenia in offspring.

Methods: This report describes a nationwide population-based cohort study from 1997 to 2013. Data from Taiwan's National Health Insurance Research Database were utilized to answer the research question. A total of 17,649 offspring with schizophrenia were selected from 11 million offspring in the general population. Additionally, we established the offspring without schizophrenia as the comparison group by matching the study cohort by age, gender in a 1:4 ratio (n = 70,596).

Results: The median age at first presentation with schizophrenia was 20 years (interquartile range (IQR), 17 to 24). Comparison of the schizophrenia and non-schizophrenia groups indicated that father's age at birth (30.0 (IQR), 27 to 33 vs. 29.0 (IQR), 26 to 32 years), mother's age at birth (26.0 (IQR), 24 to 29 vs. 26.0 (IQR), 23 to 29 years), paternal schizophrenia (2.6% vs. 0.6%), and maternal schizophrenia (4.4% vs. 0.7%) were all significantly greater in the schizophrenia group. In addition, each 5-year increase in father's age increased the odds of being diagnosed with schizophrenia (model 1: aOR = 1.22; 95% CI 1.20, 1.24; model 2: aOR = 1.20; 95% CI 1.18, 1.23). Subgroup analysis showed that each 5-year increase in father's age increased the odds of being diagnosed with schizophrenia in male and female offspring, as well as in offspring of mothers and fathers with or without schizophrenia (aOR = 1.20 to 2.20, all p values < 0.01).

Conclusion: This study indicated that advanced paternal age increased the risk of schizophrenia in offspring. Offspring born to fathers older by 5-year increments were at heightened risk of schizophrenia.

Keywords: Cumulative risk; Offspring; Paternal age; Schizophrenia.

MeSH terms

  • Adolescent
  • Adult
  • Cohort Studies
  • Fathers
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mothers
  • Paternal Age*
  • Risk Factors
  • Schizophrenia / epidemiology
  • Schizophrenia / genetics*
  • Schizophrenia / physiopathology
  • Young Adult