Paternal-age-related de novo mutations and risk for five disorders View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-07-10

AUTHORS

Jacob L. Taylor, Jean-Christophe P. G. Debost, Sarah U. Morton, Emilie M. Wigdor, Henrike O. Heyne, Dennis Lal, Daniel P. Howrigan, Alex Bloemendal, Janne T. Larsen, Jack A. Kosmicki, Daniel J. Weiner, Jason Homsy, Jonathan G. Seidman, Christine E. Seidman, Esben Agerbo, John J. McGrath, Preben Bo Mortensen, Liselotte Petersen, Mark J. Daly, Elise B. Robinson

ABSTRACT

There are established associations between advanced paternal age and offspring risk for psychiatric and developmental disorders. These are commonly attributed to genetic mutations, especially de novo single nucleotide variants (dnSNVs), that accumulate with increasing paternal age. However, the actual magnitude of risk from such mutations in the male germline is unknown. Quantifying this risk would clarify the clinical significance of delayed paternity. Using parent-child trio whole-exome-sequencing data, we estimate the relationship between paternal-age-related dnSNVs and risk for five disorders: autism spectrum disorder (ASD), congenital heart disease, neurodevelopmental disorders with epilepsy, intellectual disability and schizophrenia (SCZ). Using Danish registry data, we investigate whether epidemiologic associations between each disorder and older fatherhood are consistent with the estimated role of dnSNVs. We find that paternal-age-related dnSNVs confer a small amount of risk for these disorders. For ASD and SCZ, epidemiologic associations with delayed paternity reflect factors that may not increase with age. More... »

PAGES

3043

References to SciGraph publications

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    10

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-019-11039-6

    DOI

    http://dx.doi.org/10.1038/s41467-019-11039-6

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1117871867

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31292440


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