A landmark scientific publication produced by the NIHR BioResource and its partners - “Whole-Genome Sequencing of Patients with Rare Diseases in a National Health System” - is among the ten key advances of 2020 identified by a leading American journal.
Since 2019, the American Journal of Human Genetics has chronicled “ten key advances in applying genomic information to clinical care”.
The citation recognises the way in which the BioResource work “demonstrates the potential value of WGS [whole-genome sequencing] across a national health system, leading the NHS to plan to increase the availability of WGS-based diagnostics for rare diseases”.
“This study has shown how whole-genome sequencing can drastically shorten the diagnostic odyssey and reveal new treatments for families with rare diseases," says Professor Patrick Chinnery, co-Chair of the NIHR BioResource and Head of the Department of Clinical Neurosciences at the University of Cambridge.
Criteria for inclusion in the top ten include: using patients’ individual genomic variant information in clinical decision-making; showing impact of direct clinical implementation; and being likely to have implications for healthcare systems.
“That the paper on Whole Genome Sequencing of Patients with Rare Diseases in a National Health Systemhas been selected by American Journal of Human Genetics as one of the most impactful ones in 2020 is a recognition of the Herculean efforts made by the NIHR BioResource team and hundreds of doctors in the NHS,” says Dr Nathalie Kingston, Director of the NIHR BioResource.
“The participation of thousands of patients across the country in this pioneering genomics study has laid the foundation for the use of whole genome sequencing as a rapid diagnostic test for patients with rare diseases.”
The study, funded principally by the National Institute for Health Research, was huge: the team sequenced entire genomes of almost 10,000 NHS patients with rare diseases; they found more than 172 million genetic differences in the genomes of the patients, many of which were previously unknown.
Working with 57 NHS hospitals specialising in rare diseases, the team found 95 genes in which rare genetic differences are very likely to be a cause of rare disease. Genetic differences in at least 79 of these genes have been shown definitively to cause disease.
Importantly, the study could also discover variants in the genetic ‘on-off and dimmer switches’ in the genome that affect activity of genes. These important differences are found only by the approach taken in the BioResource work.
“This study underpinned the UK’s 100,000 genomes project which went on to provide the evidence base for integration of whole genome sequencing into routine clinical care in the NHS,” says Dr Louise Wood, Director of Science, Research and Evidence at the Department of Health and Social Care (DHSC).
“Rare diseases patients and their carers tell us one of their top priorities is getting a diagnosis. This research showed significant progress can be made addressing this ask.”
In part from lessons from this study, whole-genome sequencing will be phased in across the UK as the standard of care for diagnosis of rare diseases.
The systems developed under the study will support hastened diagnosis for patients, reduced costs for health services and improved provision of treatment.
At the time of publication, Professor Willem Ouwehand, Professor of Experimental Haematology at the University of Cambridge, the National Institute for Health Research BioResource and NHS Blood and Transplant Principal Investigator, said: “Around 40,000 children are born each year with a rare inherited disease in the UK alone. Sadly, it takes more than two years, on average, for them to be diagnosed.
“This research shows that quicker and better genetic diagnosis will be possible for more NHS patients.”
The 2020 Report in AJHG
American Journal of Human Genetics Genomic Medicine Year in Review: 2020.
Criteria of the review
Criteria for Inclusion of Papers in Genomic Medicine Year in Review 2019 and 2020
- Involve use of patients’ individual genomic variant information in clinical decision-making
- Demonstrate impact of direct clinical implementation
- Are likely to be generalizable beyond original setting
- Are likely to have implications for healthcare systems or practice guidelines
- Are of sufficient size to be robust to sampling error
- Are broadly representative of the field beyond NHGRI-sponsored or US-funded programs
Original research papers
Turro E, Astle WJ, Megy K et al. Whole-genome sequencing of patients with rare diseases in a national health system. Nature 583, 96–102 (2020). https://doi.org/10.1038/s41586-020-2434-2
Thaventhiran JED, Lango Allen H, Burren OS et al. Whole-genome sequencing of a sporadic primary immunodeficiency cohort. Nature 583, 90–95 (2020). https://doi.org/10.1038/s41586-020-2265-1
First published on 23 December 2020