Journal article

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

Jacob Gratten, Naomi R Wray, Wouter J Peyrot, John J McGrath, Peter M Visscher, Michael E Goddard

NATURE GENETICS | NATURE PUBLISHING GROUP | Published : 2016

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 th..

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University of Melbourne Researchers

Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by Australian Research Council


Awarded by NHMRC


Awarded by John Cade Fellowship from NHMRC


Funding Acknowledgements

This work was supported by Australian National Health and Medical Research Council (NHMRC) grants to N.R.W. and J.G. (1087889) and to J.G. and P.M.V. (1067795 and 1103418) and by Australian Research Council grant DP130100563 to M.E.G. N.R.W. is supported by an NHMRC Principal Research Fellowship (1078901), P.M.V. is supported by an NHMRC Senior Principal Research Fellowship (1078037), and J.J.M. is supported by grant 1056929 from the John Cade Fellowship from the NHMRC.