Taylor, Jacob L., Debost, Jean-Christophe P. G., Morton, Sarah U., Wigdor, Emilie M., Heyne, Henrike O., Lal, Dennis, Howrigan, Daniel P., Bloemendal, Alex, Larsen, Janne T., Kosmicki, Jack A., Weiner, Daniel J., Homsy, Jason, Seidman, Jonathan G., Seidman, Christine E., Agerbo, Esben ORCID: 0000-0002-2849-524X, McGrath, John J., Mortensen, Preben Bo, Petersen, Liselotte, Daly, Mark J. and Robinson, Elise B. (2019). Paternal-age-related de novo mutations and risk for five disorders. Nat. Commun., 10. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Taylor, Jacob L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Debost, Jean-Christophe P. G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morton, Sarah U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wigdor, Emilie M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heyne, Henrike O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lal, DennisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Howrigan, Daniel P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bloemendal, AlexUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Larsen, Janne T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kosmicki, Jack A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weiner, Daniel J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Homsy, JasonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seidman, Jonathan G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seidman, Christine E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Agerbo, EsbenUNSPECIFIEDorcid.org/0000-0002-2849-524XUNSPECIFIED
McGrath, John J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mortensen, Preben BoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petersen, LiselotteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daly, Mark J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robinson, Elise B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-135278
DOI: 10.1038/s41467-019-11039-6
Journal or Publication Title: Nat. Commun.
Volume: 10
Date: 2019
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
UNITED-STATES; AUTISM; SCHIZOPHRENIA; PREVALENCE; VARIANTS; SUPPORTMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13527

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