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Original research
Contribution of de novo and inherited rare CNVs to very preterm birth
  1. Hilary S Wong1,
  2. Megan Wadon2,
  3. Alexandra Evans2,
  4. George Kirov2,
  5. Neena Modi3,
  6. Michael C O'Donovan2,
  7. Anita Thapar2
  1. 1 Department of Paediatrics, Cambridge University, Cambridge, UK
  2. 2 MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
  3. 3 Section of Neonatal Medicine, Imperial College London, London, UK
  1. Correspondence to Professor Anita Thapar, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, South Glamorgan CF24 2FN, UK; thapar{at}


Background The genomic contribution to adverse health sequelae in babies born very preterm (<32 weeks’ gestation) is unknown. We conducted an investigation of rare CNVs in infants born very preterm as part of a study to determine the feasibility and acceptability of a larger, well-powered genome-wide investigation in the UK, with follow-up using linked National Health Service records and DNA storage for additional research.

Methods We studied 488 parent–offspring trios. We performed genotyping using Illumina Infinium OmniExpress Arrays. CNV calling and quality control (QC) were undertaken using published protocols. We examined de novo CNVs in infants and the rate of known pathogenic variants in infants, mothers and fathers and compared these with published comparator data. We defined rare pathogenic CNVs as those consistently reported to be associated with clinical phenotypes.

Results We identified 14 de novo CNVs, representing a mutation rate of 2.9%, compared with 2.1% reported in control populations. The median size of these CNV was much higher than in comparator data (717 kb vs 255 kb). The rate of pathogenic CNVs was 4.3% in infants, 2.7% in mothers and 2% in fathers, compared with 2.3% in UK Biobank participants.

Conclusion Our findings suggest that the rate of de novo CNVs, especially rare pathogenic CNVs, could be elevated in those born very preterm. However, we will need to conduct a much larger study to corroborate this conclusion.

  • microarray
  • molecular genetics
  • copy-number
  • developmental

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  • HSW and MW are joint first authors.

  • Twitter @hilaryswong, @na

  • Contributors NM and AT conceptualised this study; NM, AT, MCO and HSW designed the study; AT, MCO, NM and HSW obtained funding. HSW coordinated the clinical aspects including sample collection; MW wrote the first draft of the manuscript supervised by AT and MCO, and edited by NM; CNVs were called by AE; CNV analyses were overseen and supervised by GK; all authors contributed to the editing of the manuscript and approved the final version.

  • Funding This pilot study was funded by the Medical Research Council, UK (reference MR/N025288/1).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. Anonymised participant data may be available for reuse, subjected to research ethics committee approval. Request to be made to the corresponding author.