Purpose

To investigate whether increased parental age is associated with an increased risk for de novo copy number variant (CNV) formation in offspring.

Methods

CNV calls from 2323 individuals referred to Signature Genomic Laboratories for clinical microarray-based comparative genomic hybridization were investigated; 17% of the samples were prenatal and 83% were postnatal. The de novo CNV data were further split into de novo CNVs bound by low copy repeats (LCRs) and those not bound by LCRs.

Results

No association was found between CNV occurrence and paternal age in both the prenatal (p = 0.6795) and postnatal (p = 0.1741) cohorts. Maternal age was significantly higher with de novo CNV occurrence in our postnatal cohort (p = 0.0126), an effect which may be driven by formation of de novo CNVs that are bound by LCRs (p = 0.0026). Furthermore, a significant positive correlation was observed between maternal age and de novo CNVs (Point-Biserial R² = 0.0503, p = 0.0152).

Conclusions

This large-scale study did not find any evidence for the influence of increased paternal age on de novo CNV formation, while increased maternal age appeared to increase risk for de novo, non-complex CNV occurrence in offspring with intellectual disability/developmental delay. Further studies and continued technological advances will help yield more information on the risk factors for de novo CNVs.

中文翻译：

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从头复制号码的变体和父母的年龄：是否存在关联？

目的

为了调查是否增加父母的年龄与风险增加相关的从头后代的拷贝数变异（CNV）的形成。

方法

调查了来自2323名个体的CNV呼叫，这些个体被称为特征基因组实验室，用于基于临床微阵列的比较基因组杂交。样本中有17％为产前，83％为产后。在从头CNV数据进一步分割为从头CNV的结合由低拷贝重复（LCR的）和未通过的LCR的约束。

结果

在产前（p = 0.6795）和产后（p = 0.1741）队列中，CNV的发生与父亲年龄之间没有关联。在我们的产后队列中，从头发生CNV的产妇年龄要高得多（p = 0.0126），这种影响可能是由形成由LCR结合的从头CNV引起的（p = 0.0026）。此外，在产妇年龄和新生CNV之间观察到显着正相关（Point-Biserial R ²  = 0.0503，p = 0.0152）。

结论

这项大规模研究没有发现任何证据表明父本年龄增加对新生CNV形成的影响，而孕产妇年龄的增加似乎增加了新生后非复杂CNV发生的风险，该后代具有智力障碍/发育迟缓。进一步的研究和持续的技术进步将有助于提供有关从头CNV危险因素的更多信息。