title: Increased paternal age and the influence on burden of genomic copy number variation in the general population.
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.
authors: Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. J.E.Buizer@umcutrecht.nl
authors: Jacobine E
authors: JE
authors: Buizer-Voskamp
authors: Hylke M
authors: HM
authors: Blauw
authors: Marco P M
authors: MP
authors: Boks
authors: Kristel R
authors: KR
authors: van Eijk
authors: Jan H
authors: JH
authors: Veldink
authors: Eric A M
authors: EA
authors: Hennekam
authors: Jacob A S
authors: JA
authors: Vorstman
authors: Flip
authors: F
authors: Mulder
authors: Henning
authors: H
authors: Tiemeier
authors: André G
authors: AG
authors: Uitterlinden
authors: Lambertus A
authors: LA
authors: Kiemeney
authors: Leonard H
authors: LH
authors: van den Berg
authors: René S
authors: RS
authors: Kahn
authors: Chiara
authors: C
authors: Sabatti
authors: Roel A
authors: RA
authors: Ophoff
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000465:Algorithms; D056915:DNA Copy Number Variations; D005260:Female; D005828:Genetics, Population; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D009426:Netherlands; D010290:Parents; D020641:Polymorphism, Single Nucleotide