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Paternal age and schizophrenia: a population based cohort study

BMJ 2004; 329 doi: https://doi.org/10.1136/bmj.38243.672396.55 (Published 04 November 2004) Cite this as: BMJ 2004;329:1070
  1. Attila Sipos, honorary senior clinical lecturer in psychiatry1,
  2. Finn Rasmussen (finn.rasmussen{at}phs.ki.se), senior clinical lecturer and associate professor of epidemiology2,
  3. Glynn Harrison, professor of mental health1,
  4. Per Tynelius, senior statistician2,
  5. Glyn Lewis, professor of psychiatric epidemiology1,
  6. David A Leon, professor of epidemiology3,
  7. David Gunnell, professor of epidemiology4
  1. 1 Academic Unit of Psychiatry, Cotham House, University of Bristol BS6 6JL
  2. 2 Department of Public Health Sciences, Karolinska Institute, Norrbacka, SE-17176 Stockholm, Sweden
  3. 3 Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT
  4. 4 Department of Social Medicine, Canynge Hall, Bristol BS8 2PR
  1. Correspondence to: F Rasmussen
  • Accepted 4 August 2004

Abstract

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.

Footnotes

  • Contributors DG, FR, and GH developed the core idea, and FR, AS, DG, GH, GL, DAL, and PT were involved in the design of the study. DG, FR, GH, GL, and DAL raised the research funds. PT prepared the cohort data and did the database linkages. AS carried out the statistical analysis and literature search and wrote the first draft of the paper. DG, DAL, and GL gave advice on statistical methodology. All authors critically reviewed and contributed to the final draft of the paper. FR and AS are guarantors.

  • Funding Stanley Medical Research Institute.

  • Competing interests None declared.

  • Ethical approval The ethics committee at the Karolinska Institute, Stockholm, Sweden approved this study.

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