The 100,000 Genomes Pilot on rare disease diagnosis in healthcare - preliminary report

Accepted/In Press date: 6 August 2021

Published date: 11 November 2021

Additional Information: Supported by the NIHR, the Wellcome Trust, the Medical Research Council (MRC), Cancer Research U.K., the Department of Health and Social Care, and NHS England. The NIHR Bio- Resource is funded by the NIHR. Drs. Caulfield and Ouwehand are NIHR senior investigators. Dr. Chinnery is a Wellcome Trust Principal Research Fellow (212219/Z/18/Z) and an NIHR Senior Investigator who receives support from the MRC Mitochondrial Biology Unit (MC_UU_00015/9), the MRC International Centre for Genomic Medicine in Neuromuscular Disease (MR/S005021/1), and the NIHR Biomedical Research Centre (BRC). Dr. Wedderburn’s work is supported by grants from Versus Arthritis (21593), the NIHR BRC at Great Ormond Street Hospital, and the MRC (MR/ R013926/1). Drs. Smedley, Cacheiro, and Cipriani receive sup- port from the National Institutes of Health (NIH, grant 5-UM1- HG006370). Dr. Smedley’s team that performed much of the analysis was supported by grants from the NIH (1R24OD011883, U54 HG006370, and 1R01HD103805-01). Dr. Arno’s work is sup- ported by a Fight for Sight (United Kingdom) Early Career Inves- tigator Award (5045/46), NIHR BRC at Great Ormond Street Hospital Institute for Child Health, and Moorfields Eye Charity (Stephen and Elizabeth Archer in memory of Marion Woods). The Moorfields–University College London (UCL) Institute of Ophthalmology team is additionally funded by NIHR BRC at Moorfields Eye Hospital and UCL Institute of Ophthalmology. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank the personnel at NIHR BioResource for their part- nership in this study; all the health care teams at Addenbrooke’s Hospital in Cambridge, Great Ormond Street Hospital NHS Foundation Trust, University College London NHS Foundation Trust, Guy’s and St. Thomas’ Hospital, Barts Health, Oxford Uni- versity Hospitals NHS Foundation Trust, Manchester University NHS Foundation Trust, and the Newcastle Hospitals NHS Foun- dation Trust; the NHS patients and their families who made this work possible; all those across the world who have contributed to the PanelApp knowledge base and to the validation and re- porting working group (Dr. Dom McMullan, Dr. Helen Firth, Dr. Steve Abbs, and Dr. Sian Ellard) for their role in supporting the development of the bioinformatics pipeline and reporting pro- cess; Dr. David Bick and Dr. Gil McVean for providing feedback on our work; Dr. Dame Sue Hill and the team at NHS England for the work to fund and establish the 13 GMCs, which enabled the NHS contribution that included the clinical return of results within the NHS in a standardized and validated format that led to the confirmation of the diagnoses, provided additional in- formation, and led to the patient benefit reported; the Illumina Laboratory Services team at Hinxton for genome sequencing and secondary analysis; and the developers of the Human Phenotype Ontology (Monarch Initiative) and Exomiser (funded by the NIH Office of the Director [1R24OD011883]) for the support that was provided through these resources.

Local EPrints ID: 450894

URI: http://eprints.soton.ac.uk/id/eprint/450894

DOI: doi:10.1056/NEJMoa2035790

ISSN: 0028-4793

PURE UUID: 2d6b913d-3c47-41c6-884d-6e547946f730

ORCID for Eleanor Seaby: orcid.org/0000-0002-6814-8648

ORCID for Karen Temple: orcid.org/0000-0002-6045-1781

Date deposited: 19 Aug 2021 16:30

Last modified: 17 Mar 2024 04:05