Risk of psychiatric illness from advanced paternal age is not predominantly from de novo mutations

Gratten, Jacob, Wray, Naomi R., Peyrot, Wouter J., McGrath, John J., Visscher, Peter M. and Goddard, Michael E. (2016) Risk of psychiatric illness from advanced paternal age is not predominantly from de novo mutations. Nature Genetics, 48 7: 718-+. doi:10.1038/ng.3577


Author Gratten, Jacob
Wray, Naomi R.
Peyrot, Wouter J.
McGrath, John J.
Visscher, Peter M.
Goddard, Michael E.
Title Risk of psychiatric illness from advanced paternal age is not predominantly from de novo mutations
Formatted title
Risk of psychiatric illness from advanced paternal age is not predominantly from de novo mutations
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1546-1718
1061-4036
Publication date 2016-05-23
Year available 2016
Sub-type Article (original research)
DOI 10.1038/ng.3577
Open Access Status Not yet assessed
Volume 48
Issue 7
Start page 718
End page +
Total pages 9
Place of publication New York, NY United States
Publisher Nature Publishing Group
Language eng
Subject 1311 Genetics
Abstract 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.
Keyword Autism Spectrum Disorders
Bipolar Disorder
Germline Mutation
Common Variation
Familial Risk
Schizophrenia
Population
Rates
Determinants
Architecture
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID DP130100563
Institutional Status UQ

 
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