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Paternal age at childbearing and offspring psychiatric and academic morbidity
Department of Psychological and Brain Sciences, Indiana University, Bloomington, United States.
Department of Psychological and Brain Sciences, Indiana University, Bloomington, United States.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden .
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden .
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2014 (English)In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 71, no 4, 432-438 p.Article in journal (Refereed) Published
Abstract [en]

Importance: Advancing paternal age is associated with increased genetic mutations during spermatogenesis, which research suggests may cause psychiatric morbidity in the offspring. The effects of advancing paternal age at childbearing on offspring morbidity remain unclear, however, because of inconsistent epidemiologic findings and the inability of previous studies to rigorously rule out confounding factors.

Objective: To examine the associations between advancing paternal age at childbearing and numerous indexes of offspring morbidity.

Design, setting and participants: We performed a population-based cohort study of all individuals born in Sweden in 1973-2001 (N = 2,615,081), with subsets of the data used to predict childhood or adolescent morbidity. We estimated the risk of psychiatric and academic morbidity associated with advancing paternal age using several quasi-experimental designs, including the comparison of differentially exposed siblings, cousins, and first-born cousins.

Exposure: Paternal age at childbearing.

Main outcomes and measures: Psychiatric (autism, attention-deficit/hyperactivity disorder, psychosis, bipolar disorder, suicide attempt, and substance use problem) and academic (failing grades and low educational attainment) morbidity.

Results: In the study population, advancing paternal age was associated with increased risk of some psychiatric disorders (eg, autism, psychosis, and bipolar disorders) but decreased risk of the other indexes of morbidity. In contrast, the sibling-comparison analyses indicated that advancing paternal age had a dose-response relationship with every index of morbidity, with the magnitude of the associations being as large or larger than the estimates in the entire population. Compared with offspring born to fathers 20 to 24 years old, offspring of fathers 45 years and older were at heightened risk of autism (hazard ratio [HR] = 3.45; 95% CI, 1.62-7.33), attention-deficit/hyperactivity disorder (HR = 13.13; 95% CI, 6.85-25.16), psychosis (HR = 2.07; 95% CI, 1.35-3.20), bipolar disorder (HR = 24.70; 95% CI, 12.12-50.31), suicide attempts (HR = 2.72; 95% CI, 2.08-3.56), substance use problems (HR = 2.44; 95% CI, 1.98-2.99), failing a grade (odds ratio [OR] = 1.59; 95% CI, 1.37-1.85), and low educational attainment (OR = 1.70; 95% CI, 1.50-1.93) in within-sibling comparisons. Additional analyses using several quasi-experimental designs obtained commensurate results, further strengthening the internal and external validity of the findings.

Conclusions and relevance: Advancing paternal age is associated with increased risk of psychiatric and academic morbidity, with the magnitude of the risks being as large or larger than previous estimates. These findings are consistent with the hypothesis that new genetic mutations that occur during spermatogenesis are causally related to offspring morbidity.

Place, publisher, year, edition, pages
Chicago, United States: American Medical Association , 2014. Vol. 71, no 4, 432-438 p.
National Category
Medical and Health Sciences Psychiatry
Identifiers
URN: urn:nbn:se:oru:diva-54602DOI: 10.1001/jamapsychiatry.2013.4525ISI: 000335926500014PubMedID: 24577047Scopus ID: 2-s2.0-84898606763OAI: oai:DiVA.org:oru-54602DiVA: diva2:1064429
Funder
Swedish Research Council
Note

Funding Agencies:

National Institute of Child Health and Human Development 

Swedish Council for Working Life and Social Research 

Available from: 2017-01-12 Created: 2017-01-12 Last updated: 2017-01-27Bibliographically approved

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CiteExportLink to record
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