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Parental age and risk of schizophrenia: a case-control study.

Abstract

BACKGROUND

Advanced paternal age has been suggested as a possible risk factor for schizophrenia. It is not known whether this is explained by known risk factors for schizophrenia, including sibship characteristics, death of a parent before first hospital admission, season and place of birth, and family history of psychiatric illness, or by socioeconomic factors. We investigated the risk of schizophrenia associated with parental age, adjusting for known risk factors for schizophrenia, including family psychiatric history, and controlling for socioeconomic and demographic factors.

METHODS

We performed a national population, nested, case-control study based on Danish longitudinal register data. The sample included 7704 patients with an ICD-8 or ICD-10 diagnosis of schizophrenia admitted to a psychiatric facility between 1981 and 1998 in Denmark, and 192 590 individually time-, age-, and sex-matched population controls, their parents, and siblings. The risk of schizophrenia associated with increasing parental age was investigated using conditional logistic regression and controlling for family socioeconomic and demographic factors and family psychiatric history.

RESULTS

Advanced paternal and maternal age was associated with increased risk of schizophrenia in univariate analyses. Controlling for socioeconomic factors and family psychiatric history, increased risk of schizophrenia was identified in those with a paternal age of 50 years or older. Sex-specific analyses revealed that the risk of schizophrenia was increased for males with fathers 55 years or older (incidence rate ratio [IRR], 2.10; 95% confidence interval [CI], 1.35-3.28); for females, the risk associated with paternal age was substantial for fathers aged 50 to 54 years (IRR, 2.22; 95% CI, 1.44-3.44) and 55 years or older (IRR, 3.53; 95% CI, 1.82-6.83).

CONCLUSION

Increased risk of schizophrenia was associated with advanced paternal age, particularly in females, lending support to the theory that de novo mutations, possibly X-linked, associated with increased parental age might be responsible for some cases of schizophrenia.

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  • Authors+Show Affiliations

    ,

    National Centre for Register-based Research, Aarhus University, Aarhus, Denmark. mb@ncrr.dk

    , , ,

    Source

    Archives of general psychiatry 60:7 2003 Jul pg 673-8

    MeSH

    Adult
    Age Factors
    Case-Control Studies
    Denmark
    Family Health
    Female
    Genetic Diseases, X-Linked
    Genetic Predisposition to Disease
    Humans
    Incidence
    Logistic Models
    Male
    Maternal Age
    Mental Disorders
    Middle Aged
    Mutation
    Parents
    Paternal Age
    Registries
    Risk Factors
    Schizophrenia
    Sex Factors

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    12860771

    Citation

    Byrne, Majella, et al. "Parental Age and Risk of Schizophrenia: a Case-control Study." Archives of General Psychiatry, vol. 60, no. 7, 2003, pp. 673-8.
    Byrne M, Agerbo E, Ewald H, et al. Parental age and risk of schizophrenia: a case-control study. Arch Gen Psychiatry. 2003;60(7):673-8.
    Byrne, M., Agerbo, E., Ewald, H., Eaton, W. W., & Mortensen, P. B. (2003). Parental age and risk of schizophrenia: a case-control study. Archives of General Psychiatry, 60(7), pp. 673-8.
    Byrne M, et al. Parental Age and Risk of Schizophrenia: a Case-control Study. Arch Gen Psychiatry. 2003;60(7):673-8. PubMed PMID: 12860771.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Parental age and risk of schizophrenia: a case-control study. AU - Byrne,Majella, AU - Agerbo,Esben, AU - Ewald,Henrik, AU - Eaton,William W, AU - Mortensen,Preben Bo, PY - 2003/7/16/pubmed PY - 2003/9/17/medline PY - 2003/7/16/entrez SP - 673 EP - 8 JF - Archives of general psychiatry JO - Arch. Gen. Psychiatry VL - 60 IS - 7 N2 - BACKGROUND: Advanced paternal age has been suggested as a possible risk factor for schizophrenia. It is not known whether this is explained by known risk factors for schizophrenia, including sibship characteristics, death of a parent before first hospital admission, season and place of birth, and family history of psychiatric illness, or by socioeconomic factors. We investigated the risk of schizophrenia associated with parental age, adjusting for known risk factors for schizophrenia, including family psychiatric history, and controlling for socioeconomic and demographic factors. METHODS: We performed a national population, nested, case-control study based on Danish longitudinal register data. The sample included 7704 patients with an ICD-8 or ICD-10 diagnosis of schizophrenia admitted to a psychiatric facility between 1981 and 1998 in Denmark, and 192 590 individually time-, age-, and sex-matched population controls, their parents, and siblings. The risk of schizophrenia associated with increasing parental age was investigated using conditional logistic regression and controlling for family socioeconomic and demographic factors and family psychiatric history. RESULTS: Advanced paternal and maternal age was associated with increased risk of schizophrenia in univariate analyses. Controlling for socioeconomic factors and family psychiatric history, increased risk of schizophrenia was identified in those with a paternal age of 50 years or older. Sex-specific analyses revealed that the risk of schizophrenia was increased for males with fathers 55 years or older (incidence rate ratio [IRR], 2.10; 95% confidence interval [CI], 1.35-3.28); for females, the risk associated with paternal age was substantial for fathers aged 50 to 54 years (IRR, 2.22; 95% CI, 1.44-3.44) and 55 years or older (IRR, 3.53; 95% CI, 1.82-6.83). CONCLUSION: Increased risk of schizophrenia was associated with advanced paternal age, particularly in females, lending support to the theory that de novo mutations, possibly X-linked, associated with increased parental age might be responsible for some cases of schizophrenia. SN - 0003-990X UR - https://www.unboundmedicine.com/medline/citation/12860771/full_citation L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=12860771.ui DB - PRIME DP - Unbound Medicine ER -