Abstract
Genomic copy number variations (CNVs) and increased parental age are both associated with the risk to develop a variety of clinical neuropsychiatric disorders such as autism, schizophrenia and bipolar disorder. At the same time, it has been shown that the rate of transmitted de novo single nucleotide mutations is increased with paternal age. To address whether paternal age also affects the burden of structural genomic deletions and duplications, we examined various types of CNV burden in a large population sample from the Netherlands. Healthy participants with parental age information (n = 6,773) were collected at different University Medical Centers. CNVs were called with the PennCNV algorithm using Illumina genome-wide SNP array data. We observed no evidence in support of a paternal age effect on CNV load in the offspring. Our results were negative for global measures as well as several proxies for de novo CNV events in this unique sample. While recent studies suggest de novo single nucleotide mutation rate to be dominated by the age of the father at conception, our results strongly suggest that at the level of global CNV burden there is no influence of increased paternal age. While it remains possible that local genomic effects may exist for specific phenotypes, this study indicates that global CNV burden and increased father’s age may be independent disease risk factors.
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Acknowledgments
We gratefully acknowledge the contribution of the participants. Data was obtained from different studies that were previously supported by The Netherlands Organization for Scientific Research (NWO), the Prinses Beatrix Fonds, VSB Fonds, the Research Institute for Diseases in the Elderly, the Netherlands Genomics Initiative, the National Institute for Mental Health (NIMH), The National Institute for Drug Abuse (NIDA), the European Commission, and the Radboud University Nijmegen Medical Center, the Erasmus Medical Center Rotterdam, and the University Medical Center Utrecht in The Netherlands. We thank Nelson Freimer for critically reading the manuscript. The authors report no biomedical financial interest or potential conflicts of interest.
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The authors have no conflicts of interest with this work.
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This study complies with the current laws of the Netherlands.
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The authors J. E. Buizer-Voskamp, H. M. Blauw and M. P. M. Boks have contributed equally.
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Buizer-Voskamp, J.E., Blauw, H.M., Boks, M.P.M. et al. Increased paternal age and the influence on burden of genomic copy number variation in the general population. Hum Genet 132, 443–450 (2013). https://doi.org/10.1007/s00439-012-1261-4
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DOI: https://doi.org/10.1007/s00439-012-1261-4