Intended for healthcare professionals

Analysis

Challenges of using whole genome sequencing in population newborn screening

BMJ 2024; 384 doi: https://doi.org/10.1136/bmj-2023-077060 (Published 05 March 2024) Cite this as: BMJ 2024;384:e077060

Linked Opinion

Helen Salisbury: The Generation Study

  1. Rachel Horton, clinical research fellow1,
  2. Caroline F Wright, professor2,
  3. Helen V Firth, consultant in clinical genetics and genomic medicine3,
  4. Clare Turnbull, consultant in cancer genetics4,
  5. Robin Lachmann, consultant5,
  6. Richard S Houlston, head of division genetics and epidemiology4,
  7. Anneke Lucassen, professor of genomic medicine1
  1. 1Centre for Human Genetics, University of Oxford, Oxford, UK
  2. 2Department of Clinical and Biomedical Sciences (Medical School), University of Exeter, Exeter, UK
  3. 3Cambridge University Hospitals, Cambridge, UK
  4. 4Institute of Cancer Research, London, UK
  5. 5University College London Hospitals NHS Trust National Hospital for Neurology and Neurosurgery, London, UK
  1. Correspondence to: A Lucassen anneke.lucassen{at}ndm.ox.ac.uk

Rachel Horton and colleagues argue that making sense of genomic variation in newborn babies is difficult, so the UK Generation Study will analyse only a tiny proportion of the genome. Why then is it collecting entire genomes?

In the UK, newborn screening is offered under the oversight of the National Screening Committee.1 Heel prick blood spots are currently tested biochemically for nine conditions for which early treatment, before symptoms, improves outcome. The NHS embedded Newborn Genomes Programme (recently renamed the Generation Study) aims to “detect hundreds more rare, treatable diseases in [the] first years of life”2 and builds on the ambition outlined by the UK health secretary in 2019 “that eventually every child will be able to receive whole genome sequencing along with the heel prick test … We will give every child the best possible start in life.”3

The Generation Study aims to screen at least 100 000 newborn babies for several hundred potentially treatable rare diseases that are likely to present by the age of 5 years. The offer of this screening will be contingent on parental consent to the baby’s genome being linked to their health records to enable research into genetic links to disease.4

In aspiring to fulfil both aims simultaneously, the Generation Study fuses separate elements: one focusing on newborn screening for rare conditions; one exploring how a baby’s genetic code relates to their life trajectory. Because these two elements are run under the same study, the newborn screening aspect cannot consider what assay would be best for that purpose alone. It has to be whole genome sequencing, even though the screening proposed could be obtained from more focused genetic testing. However, the offer of “extra” screening is likely to attract parents and overshadow considerations around the pros and cons of enrolling …

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