Whole genome sequencing for the diagnosis of neurological repeat expansion disorders in the UK: a retrospective diagnostic accuracy and prospective clinical validation study

e-pub ahead of print date: 16 February 2022

Published date: 1 March 2022

Additional Information: Funding Information: Genomics England and the 100?000 Genomes Project was funded by the National Institute for Health Research (NIHR), the Wellcome Trust, the Medical Research Council, Cancer Research UK, the Department of Health and Social Care, and NHS England. We thank all the patients and health-care teams at the 13 NHS Genomic Medicine Centres in England, where around 5000 multidisciplinary staff enrolled patients to the 100?000 Genomes Project. Patients were also enrolled to the 100?000 Genomes Project from Scotland by the Scottish Genomes Project, and across Wales and Northern Ireland. This work forms part of the portfolio of translational research at the NIHR Biomedical Research Centres at Barts, Birmingham, Bristol, Cambridge, Great Ormond Street Foundation, Guy's and St Thomas?, Imperial, Leeds, Leicester, Manchester, Maudsley, Moorfields, Newcastle, Nottingham, Oxford, Royal Marsden, Sheffield, Southampton, and University College London. This work was made possible through the generosity of NHS patients and their families and uses clinical data from the NHS and NHS Digital. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. MJC is an NIHR senior investigator. PFC 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), the Leverhulme Trust (RPG-2018?408), an MRC research grant (MR/S035699/1), and an Alzheimer's Society Project Grant (AS-PG-18b-022). AT is an MRC clinician scientist (MR/S006753/1). We thank Illumina Clinical Laboratory Sciences (San Diego, CA, USA), Illumina (San Diego, CA, USA), and Granta Park (Cambridge, UK) for undertaking whole genome sequencing and validation of true positives and negatives. We are grateful to the team at NHS England and for the work to fund and establish the 13 Genomic Medicine Centres. This enabled the NHS contribution to the 100?000 Genomes Project by enrolment of patients, receipt of the results, and, in some cases, orthogonal validation using standardised approaches, including return of findings for direct patient benefit. Funding Information: Genomics England is a company wholly owned by the UK Department of Health and Social Care and was created in 2013 to introduce whole genome sequencing into health care in conjunction with NHS England. All authors affiliated with Genomics England (KI, DP, ERAT, LCD, DK, KRS, TF, RHS, AR, MJC, and AT) are, or were, salaried by or seconded to Genomics England. RJT, MAE, ED, and RTH are employees and shareholders of Illumina. PFC is in receipt of a grant from the Wellcome Trust Medical Research Council (MRC). All other named authors declare no competing interests. Declarations of interests for members of the WGS for Neurological Diseases Group are provided in the appendix (p 14) . Funding Information: Genomics England and the 100 000 Genomes Project was funded by the National Institute for Health Research (NIHR), the Wellcome Trust, the Medical Research Council, Cancer Research UK, the Department of Health and Social Care, and NHS England. We thank all the patients and health-care teams at the 13 NHS Genomic Medicine Centres in England, where around 5000 multidisciplinary staff enrolled patients to the 100 000 Genomes Project. Patients were also enrolled to the 100 000 Genomes Project from Scotland by the Scottish Genomes Project, and across Wales and Northern Ireland. This work forms part of the portfolio of translational research at the NIHR Biomedical Research Centres at Barts, Birmingham, Bristol, Cambridge, Great Ormond Street Foundation, Guy's and St Thomas’, Imperial, Leeds, Leicester, Manchester, Maudsley, Moorfields, Newcastle, Nottingham, Oxford, Royal Marsden, Sheffield, Southampton, and University College London. This work was made possible through the generosity of NHS patients and their families and uses clinical data from the NHS and NHS Digital. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. Funding Information: MJC is an NIHR senior investigator. PFC 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), the Leverhulme Trust (RPG-2018–408), an MRC research grant (MR/S035699/1), and an Alzheimer's Society Project Grant (AS-PG-18b-022). AT is an MRC clinician scientist (MR/S006753/1). We thank Illumina Clinical Laboratory Sciences (San Diego, CA, USA), Illumina (San Diego, CA, USA), and Granta Park (Cambridge, UK) for undertaking whole genome sequencing and validation of true positives and negatives. We are grateful to the team at NHS England and for the work to fund and establish the 13 Genomic Medicine Centres. This enabled the NHS contribution to the 100 000 Genomes Project by enrolment of patients, receipt of the results, and, in some cases, orthogonal validation using standardised approaches, including return of findings for direct patient benefit. Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Copyright: Copyright 2022 Elsevier B.V., All rights reserved.

Local EPrints ID: 455528

URI: http://eprints.soton.ac.uk/id/eprint/455528

DOI: doi:10.1016/S1474-4422(21)00462-2

ISSN: 1474-4422

PURE UUID: 4eb108f7-a00d-4fd0-919e-da14b88b7af1

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

Date deposited: 24 Mar 2022 17:35

Last modified: 17 Mar 2024 02:48