Risk of psychiatric illness from advanced paternal age is not predominantly from de novo mutations
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The offspring of older fathers have higher risk of psychiatric disorders such as schizophrenia and autism. Paternal-age-related de novo mutations are widely assumed to be the underlying causal mechanism, and, although such mutations must logically make some contribution, there are alternative explanations (for example, elevated liability to psychiatric illness may delay fatherhood). We used population genetic models based on empirical observations of key parameters (for example, mutation rate, prevalence, and heritability) to assess the genetic relationship between paternal age and risk of psychiatric illness. These models suggest that age-related mutations are unlikely to explain much of the increased risk of psychiatric disorders in children of older fathers. Conversely, a model incorporating a weak correlation between age at first child and liability to psychiatric illness matched epidemiological observations. Our results suggest that genetic risk factors shared by older fathers and their offspring are a credible alternative explanation to de novo mutations for risk to children of older fathers.
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Parental age might be confounded by parents with autism traits having children later in life, or choosing partners with high autism traits.
“parental age might be confounded by parents with autism traits having children later in life, or choosing partners with high autism traits [252, 253].”
From The contribution of environmental exposure to the etiology of autism spectrum disorder (2019) · cites this paper as [253]
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- Authors
- Gratten, J., Wray, N. R., Peyrot, W. J., McGrath, J. J., Visscher, P. M., & Goddard, M. E.
- Affiliations
- The University of Queensland (AU)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- The University of Melbourne (AU)
- Corresponding author
- Gratten, Jacob
- Venue
- Nature Genetics
- Published
- 2016-05-23
- Volume
- 48
- Issue
- 7
- Pages
- 718-724
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2399862428
- Cited by
- 118
- References
- 52
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 8 · 2023: 7 · 2022: 7 · 2021: 13 · 2020: 15 · 2019: 22 · 2018: 6 · 2017: 22 · 2016: 5
- FWCI
- 16.29
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Minerva Access (University of Melbourne) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Medical Research Council (1078037, 1078901, 1103418)
- Australian Research Council (DP130100563)
- National Health and Medical Research Council (1067795, 1078901, 1087889, 1056929, 1078037, 1103418)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- advanced paternal age, de novo mutations, mental illness, schizophrenia, autism spectrum disorder, genetic susceptibility, heritability, mutation rate, population genetic models
- MeSH terms
- Age Factors, Autistic Disorder, Child, Genetic Markers, Humans, Male, Mutation, Paternal Age, Risk Factors, Schizophrenia
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