The pilot study of rare undiagnosed diseases, which analysed the genes of 4,660 people from 2,183 families,  found that using WGS led to a new diagnosis for 25% of participants. Of these new diagnoses, 14% were found in regions of the genome that would be missed by other conventional methods, including other types of non-whole genomic tests. The study was published in the New England Journal of Medicine.

All of the study participants had been early participants in the 100,000 Genomes Project. This ground-breaking project, led by Genomics England and NHS England, was established in 2013 to sequence 100,000 whole genomes from NHS patients and their families.

The pilot study, led by Genomics England and Queen Mary University of London and undertaken in partnership with the National Institute for Health Research (NIHR) BioResource, found that using WGS led to a new diagnosis for 25% of the participants. Of these new diagnoses, 14% were found in regions of the genome that would be missed by other conventional methods, including other types of non-whole genomic tests.

Many of the participants had gone through years of appointments, without getting any answers. By having their whole genome sequenced diagnoses were uncovered that would not have previously been detectable. The pilot study shows that WGS can effectively secure a diagnosis for patients, save the NHS vital resources and pave the way for other interventions.

For around a quarter of study participants, their diagnosis meant they were able to receive more focused clinical care. This included further family screening, dietary change, provision of vitamins and / or minerals and other therapies.

The study is the first to analyse the diagnostic and clinical impact of WGS for a broad range of rare diseases within a national healthcare system. The findings support its widespread adoption in health systems worldwide.

The high performance of WGS for specific conditions observed in the pilot study - including intellectual disability, vision and hearing disorders of 40-55% diagnostic yield - has underpinned the case for the inclusion of WGS to diagnose specific rare diseases as part of the new NHS National Genomic Test Directory.

The pilot study was also conducted in partnership with the National Institute for Health Research (NIHR) and Illumina who undertook the sequencing, and it was funded by the NIHR, the Wellcome Trust, the Medical Research Council, Cancer Research UK, the Department of Health and Social Care, and NHS England.

The 100,000 Genomes Project Pilot Investigators included co-author Dr Jana Vandrovcova, and colleagues from UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery (UCLH) including Dr Emer O’Connor,  Janice Yip, Katrina Newland, Professor Huw R. Morris, Dr James Polke, Professor Nicholas W. Wood and Professor Henry Houlden.

Professor Nick Wood, Professor of Clinical Genetics, UCL Queen Square Institute of Neurology, and consultant neurologist at UCLH: “This represents a tremendous milestone in dissecting a range of rare, often significantly disabling, conditions. Identifying the genes and mutations responsible empowers the patient their families and of course illuminates the causes of disease. For me, as clinician scientist, to now be able to accurately diagnose the patients who come to our clinics and guide the counselling for at risk individuals is hugely satisfying. This large-scale detailed approach allows a real opportunity for identifying new targets for therapeutic intervention.”  
Professor John Hardy, Chair of the Molecular Biology of Neurological Disease, UCL Queen Square Institute of Neurology “Whole genome sequencing at birth will become a standard part of medical practice with clear privacy safeguards as it will undoubtedly, as this report shows, lead to clear health benefits.  There are many challenges still to face however.  These include data privacy concerns and computer storage and analytis pipelines (the computer files for whole genome studies are huge and data interpretation is complex and requires specialist training).  This study is a step on the path to using genetic data to help in getting us all to better health outcomes.”

Professor Michael Hanna, Director of UCL Queen Square Institute of Neurology “ I particularly want to congratulate IoN biostatisticians and clinical colleagues, on their important contribution to this landmark paper demonstrating the power of whole genome sequencing. This technology, when combined with expert biostatisticians and clinical expertise, working in multidisciplinary teams, can transform diagnostics and ensure an accurate genetic diagnosis in more patients. The deep clinical, genetic and bioinformatic expertise at the Queen Square Institute of Neurology means we are well placed to harness this technology, and to play a leading role in developing advanced genetic therapies,  to improve the lives of patients with neurological diseases”

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