Whole-genome sequencing of patients with rare diseases in a national health system

NIHR BioResource for the 100,000 Genomes Project

doi:10.1038/s41586-020-2434-2

Whole-genome sequencing of patients with rare diseases in a national health system

NIHR BioResource for the 100,000 Genomes Project

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源语言	英语
页（从-至）	96-102
页数	7
期刊	Nature
卷	583
期	7814
DOI	https://doi.org/10.1038/s41586-020-2434-2
出版状态	已出版 - 7月 2 2020
已对外发布	是

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10.1038/s41586-020-2434-2

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@article{0c15b96d75304157b67e3806759bf82a,

title = "Whole-genome sequencing of patients with rare diseases in a national health system",

author = "{NIHR BioResource for the 100,000 Genomes Project} and Ernest Turro and Astle, {William J.} and Karyn Megy and Stefan Gr{\"a}f and Daniel Greene and Olga Shamardina and Allen, {Hana Lango} and Alba Sanchis-Juan and Mattia Frontini and Chantal Thys and Jonathan Stephens and Rutendo Mapeta and Burren, {Oliver S.} and Kate Downes and Matthias Haimel and Salih Tuna and Deevi, {Sri V.V.} and Aitman, {Timothy J.} and Bennett, {David L.} and Paul Calleja and Keren Carss and Caulfield, {Mark J.} and Chinnery, {Patrick F.} and Dixon, {Peter H.} and Gale, {Daniel P.} and Roger James and Ania Koziell and Laffan, {Michael A.} and Levine, {Adam P.} and Maher, {Eamonn R.} and Markus, {Hugh S.} and Joannella Morales and Morrell, {Nicholas W.} and Mumford, {Andrew D.} and Elizabeth Ormondroyd and Stuart Rankin and Augusto Rendon and Sylvia Richardson and Irene Roberts and Roy, {Noemi B.A.} and Saleem, {Moin A.} and Smith, {Kenneth G.C.} and Hannah Stark and Tan, {Rhea Y.Y.} and Themistocleous, {Andreas C.} and Thrasher, {Adrian J.} and Hugh Watkins and Webster, {Andrew R.} and Wilkins, {Martin R.} and Catherine Williamson",

note = "Funding Information: Acknowledgements This research was made possible through access to the data and findings generated by two pilot studies for the 100,000 Genomes Project. The enrolment was coordinated for one by the NIHR BioResource and for the other by Genomics England Ltd (GEL), a company wholly owned by the Department of Health in the United Kingdom. These pilot studies were mainly funded by grants from the NIHR in England to Cambridge University Hospitals and GEL, respectively. Additional funding was provided by the British Heart Foundation (BHF), MRC, NHS England, the Wellcome Trust and many other fund providers (see funding acknowledgements for individual researchers). The pilot studies use data provided by patients and their close relatives and collected by the NHS and other healthcare providers as part of their care and support. The vast majority of participants in the two pilot studies have been enrolled in the NIHR BioResource. We thank all volunteers for their participation and the NIHR Biomedical Research Centres (BRC), NIHR BioResource Centres, NHS Trust Hospitals, NHS Blood and Transplant and their staff for their contribution. This research has been conducted using the UK Biobank resource under Application Number 9616, granting access to DNA samples and accompanying participant data. UK Biobank has received funding from the MRC, Wellcome Trust, Department of Health, BHF, Diabetes UK, Northwest Regional Development Agency, Scottish Government and Welsh Assembly Government. The MRC and Wellcome Trust had a key role in the decision to establish the UK Biobank. A. McMahon and J. Morales are funded by The Wellcome Trust (WT200990/Z/16/Z) and the European Molecular Biology Laboratory; K.G.C.S. holds a Wellcome Investigator Award, MRC Programme Grant (number MR/ L019027/1); M.I.M. is a Wellcome Senior Investigator and receives support from the Wellcome Trust (090532, 0938381) and is a member of the DOLORisk consortium funded by the European Commission Horizon 2020 (ID633491); R. Horvath is a Wellcome Trust Investigator (109915/Z/15/Z), who receives support from the Wellcome Centre for Mitochondrial Research (203105/Z/16/Z), MRC (MR/N025431/1), the European Research Council (309548), the Wellcome Trust Pathfinder Scheme (201064/Z/16/Z), the Newton Fund (UK/Turkey, MR/N027302/1) and the European Union H2020 – Research and Innovation Actions (SC1-PM-03-2017, Solve-RD); D.L.B. is a Wellcome clinical scientist (202747/Z/16/Z) and is a member of the DOLORisk consortium funded by the European Commission Horizon 2020 (ID633491); J.S.W. is funded by Wellcome Trust [107469/Z/15/Z], NIHR Cardiovascular Biomedical Research Unit at Royal Brompton & Harefield NHS Foundation Trust and Imperial College London; A.J.T. is supported by the Wellcome Trust (104807/Z/14/Z) and the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London; L. Southgate is supported by the Wellcome Trust Institutional Strategic Support Fund (204809/Z/16/Z) awarded to St George{\textquoteright}s, University of London; M.J.D. receives funding from Wellcome Trust (WT098519MA); M.C.S. holds an MRC Clinical Research Training Fellowship (MR/ R002363/1); J.A.S. is funded by MRC UK grant MR/M012212/1; A.J.M. received funding from an MRC Senior Clinical Fellowship (MR/L006340/1); C. Lentaigne received funding from an MRC Clinical Research Training Fellowship (MR/J011711/1); M.R.W. holds a NIHR award to the NIHR Imperial Clinical Research Facility at Imperial College Healthcare NHS Trust; C. Williamson holds a NIHR Senior Investigator Award; M. A. Kurian holds a NIHR Research Professorship (NIHR-RP-2016-07-019) and Wellcome Intermediate Fellowship (098524/Z/12/A); M.J.C. is an NIHR Senior Investigator and is funded by the NIHR Barts Biomedical Research Centre; N. Cooper is partially funded by NIHR Imperial College Biomedical Research Centre; C. Hadinnapola was funded through a PhD Fellowship by the NIHR Translational Research Collaboration - Rare Diseases; A.D.M. and S.K.W. were funded by the NIHR Bristol Biomedical Research Centre; E.L.M. received funding from the NIHR Biomedical Research Centre at University College London Hospitals; K.C.G. received funding from the NIHR Great Ormond Street Biomedical Research Centre; I.R. and E. Louka are supported by the NIHR Translational Research Collaboration - Rare Diseases; J.C.T., J.M.T. and S. Patel are funded by the NIHR Oxford Biomedical Research Centre; G. Arno is funded by a Fight for Sight (UK) Early Career Investigator Award (5045-5046); All authors affiliated with Moorfields Eye hospital and Institute of Ophthalmology are funded by the NIHR Moorfields Biomedical Research Centre and UCL Institute of Ophthalmology, Fight for Sight (UK) Early Career Investigator Award, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, Foundation Fighting Blindness (USA) and Retinitis Pigmentosa Fighting Blindness; A.T.M. is funded by Retinitis Pigmentosa Fighting Blindness, P.Y.-W.-M. is supported by grants from MRC UK (G1002570), Fight for Sight (1570/1571 and 24TP171), NIHR (IS-BRC-1215-20002); S.O.B. is supported by NIHR Translational Research Collaboration - Rare Diseases (01/04/15-30/04/2017); A.R.W. works for the NIHR Moorfields Biomedical Research Centre and the UCL Institute of Ophthalmology and Moorfields Eye Hospital; the following NIHR Biomedical Research Centres contributed to the enrolment for the ICP domain: Imperial College Healthcare NHS Trust, Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust and King{\textquoteright}s College London. All authors affiliated with Moorfields Eye hospital and Institute of Ophthalmology are funded by the NIHR Biomedical Resource Centre at UCL Institute of Ophthalmology and Moorfields; A.C.T. is a member of the International Diabetic Neuropathy Consortium, the Novo Nordisk Foundation (NNF14SA0006) and is a member of the DOLORisk consortium funded by the European Commission Horizon 2020 (ID633491); J. Whitworth is a recipient of a Cancer Research UK Cambridge Cancer Centre Clinical Research Training Fellowship; S.A.J. is funded by Kids Kidney Research; D.P.G. is funded by the MRC, Kidney Research UK and St Peters Trust for Kidney, Bladder and Prostate Research; The MPGN/DDD/C3 Glomerulopathy Rare Disease Group contributed to the recruitment and analysis for the PMG domain; K.J.M. is supported by the Northern Counties Kidney Research Fund; P.H.D. receives funding from ICP Support; T.K.B. received a PhD fellowship from the NHSBT and British Society of Haematology; H.S.M. receives support from BHF Programme Grant RG/16/4/32218; A.L. is a BHF Senior Basic Science Research Fellow - FS/13/48/30453; K.F. and C.V.-G. are supported by the Research Council of the University of Leuven (BOF KU Leuven‚ Belgium; OT/14/098); H.J.B. works for the Netherlands CardioVascular Research Initiative (CVON); Fiona Cunningham, Aoife McMahon, Glen Threadgold, and Joannella Morales received funding from the Wellcome Trust (grant numbers WT108749/Z/15/Z and WT200990/Z/16/Z) and the European Molecular Biology Laboratory. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care of England or any of the other funding agencies. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2020",

month = jul,

day = "2",

doi = "10.1038/s41586-020-2434-2",

language = "English",

volume = "583",

pages = "96--102",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7814",

}

TY - JOUR

T1 - Whole-genome sequencing of patients with rare diseases in a national health system

AU - NIHR BioResource for the 100,000 Genomes Project

AU - Turro, Ernest

AU - Astle, William J.

AU - Megy, Karyn

AU - Gräf, Stefan

AU - Greene, Daniel

AU - Shamardina, Olga

AU - Allen, Hana Lango

AU - Sanchis-Juan, Alba

AU - Frontini, Mattia

AU - Thys, Chantal

AU - Stephens, Jonathan

AU - Mapeta, Rutendo

AU - Burren, Oliver S.

AU - Downes, Kate

AU - Haimel, Matthias

AU - Tuna, Salih

AU - Deevi, Sri V.V.

AU - Aitman, Timothy J.

AU - Bennett, David L.

AU - Calleja, Paul

AU - Carss, Keren

AU - Caulfield, Mark J.

AU - Chinnery, Patrick F.

AU - Dixon, Peter H.

AU - Gale, Daniel P.

AU - James, Roger

AU - Koziell, Ania

AU - Laffan, Michael A.

AU - Levine, Adam P.

AU - Maher, Eamonn R.

AU - Markus, Hugh S.

AU - Morales, Joannella

AU - Morrell, Nicholas W.

AU - Mumford, Andrew D.

AU - Ormondroyd, Elizabeth

AU - Rankin, Stuart

AU - Rendon, Augusto

AU - Richardson, Sylvia

AU - Roberts, Irene

AU - Roy, Noemi B.A.

AU - Saleem, Moin A.

AU - Smith, Kenneth G.C.

AU - Stark, Hannah

AU - Tan, Rhea Y.Y.

AU - Themistocleous, Andreas C.

AU - Thrasher, Adrian J.

AU - Watkins, Hugh

AU - Webster, Andrew R.

AU - Wilkins, Martin R.

AU - Williamson, Catherine

N1 - Funding Information: Acknowledgements This research was made possible through access to the data and findings generated by two pilot studies for the 100,000 Genomes Project. The enrolment was coordinated for one by the NIHR BioResource and for the other by Genomics England Ltd (GEL), a company wholly owned by the Department of Health in the United Kingdom. These pilot studies were mainly funded by grants from the NIHR in England to Cambridge University Hospitals and GEL, respectively. Additional funding was provided by the British Heart Foundation (BHF), MRC, NHS England, the Wellcome Trust and many other fund providers (see funding acknowledgements for individual researchers). The pilot studies use data provided by patients and their close relatives and collected by the NHS and other healthcare providers as part of their care and support. The vast majority of participants in the two pilot studies have been enrolled in the NIHR BioResource. We thank all volunteers for their participation and the NIHR Biomedical Research Centres (BRC), NIHR BioResource Centres, NHS Trust Hospitals, NHS Blood and Transplant and their staff for their contribution. This research has been conducted using the UK Biobank resource under Application Number 9616, granting access to DNA samples and accompanying participant data. UK Biobank has received funding from the MRC, Wellcome Trust, Department of Health, BHF, Diabetes UK, Northwest Regional Development Agency, Scottish Government and Welsh Assembly Government. The MRC and Wellcome Trust had a key role in the decision to establish the UK Biobank. A. McMahon and J. Morales are funded by The Wellcome Trust (WT200990/Z/16/Z) and the European Molecular Biology Laboratory; K.G.C.S. holds a Wellcome Investigator Award, MRC Programme Grant (number MR/ L019027/1); M.I.M. is a Wellcome Senior Investigator and receives support from the Wellcome Trust (090532, 0938381) and is a member of the DOLORisk consortium funded by the European Commission Horizon 2020 (ID633491); R. Horvath is a Wellcome Trust Investigator (109915/Z/15/Z), who receives support from the Wellcome Centre for Mitochondrial Research (203105/Z/16/Z), MRC (MR/N025431/1), the European Research Council (309548), the Wellcome Trust Pathfinder Scheme (201064/Z/16/Z), the Newton Fund (UK/Turkey, MR/N027302/1) and the European Union H2020 – Research and Innovation Actions (SC1-PM-03-2017, Solve-RD); D.L.B. is a Wellcome clinical scientist (202747/Z/16/Z) and is a member of the DOLORisk consortium funded by the European Commission Horizon 2020 (ID633491); J.S.W. is funded by Wellcome Trust [107469/Z/15/Z], NIHR Cardiovascular Biomedical Research Unit at Royal Brompton & Harefield NHS Foundation Trust and Imperial College London; A.J.T. is supported by the Wellcome Trust (104807/Z/14/Z) and the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London; L. Southgate is supported by the Wellcome Trust Institutional Strategic Support Fund (204809/Z/16/Z) awarded to St George’s, University of London; M.J.D. receives funding from Wellcome Trust (WT098519MA); M.C.S. holds an MRC Clinical Research Training Fellowship (MR/ R002363/1); J.A.S. is funded by MRC UK grant MR/M012212/1; A.J.M. received funding from an MRC Senior Clinical Fellowship (MR/L006340/1); C. Lentaigne received funding from an MRC Clinical Research Training Fellowship (MR/J011711/1); M.R.W. holds a NIHR award to the NIHR Imperial Clinical Research Facility at Imperial College Healthcare NHS Trust; C. Williamson holds a NIHR Senior Investigator Award; M. A. Kurian holds a NIHR Research Professorship (NIHR-RP-2016-07-019) and Wellcome Intermediate Fellowship (098524/Z/12/A); M.J.C. is an NIHR Senior Investigator and is funded by the NIHR Barts Biomedical Research Centre; N. Cooper is partially funded by NIHR Imperial College Biomedical Research Centre; C. Hadinnapola was funded through a PhD Fellowship by the NIHR Translational Research Collaboration - Rare Diseases; A.D.M. and S.K.W. were funded by the NIHR Bristol Biomedical Research Centre; E.L.M. received funding from the NIHR Biomedical Research Centre at University College London Hospitals; K.C.G. received funding from the NIHR Great Ormond Street Biomedical Research Centre; I.R. and E. Louka are supported by the NIHR Translational Research Collaboration - Rare Diseases; J.C.T., J.M.T. and S. Patel are funded by the NIHR Oxford Biomedical Research Centre; G. Arno is funded by a Fight for Sight (UK) Early Career Investigator Award (5045-5046); All authors affiliated with Moorfields Eye hospital and Institute of Ophthalmology are funded by the NIHR Moorfields Biomedical Research Centre and UCL Institute of Ophthalmology, Fight for Sight (UK) Early Career Investigator Award, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, Foundation Fighting Blindness (USA) and Retinitis Pigmentosa Fighting Blindness; A.T.M. is funded by Retinitis Pigmentosa Fighting Blindness, P.Y.-W.-M. is supported by grants from MRC UK (G1002570), Fight for Sight (1570/1571 and 24TP171), NIHR (IS-BRC-1215-20002); S.O.B. is supported by NIHR Translational Research Collaboration - Rare Diseases (01/04/15-30/04/2017); A.R.W. works for the NIHR Moorfields Biomedical Research Centre and the UCL Institute of Ophthalmology and Moorfields Eye Hospital; the following NIHR Biomedical Research Centres contributed to the enrolment for the ICP domain: Imperial College Healthcare NHS Trust, Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. All authors affiliated with Moorfields Eye hospital and Institute of Ophthalmology are funded by the NIHR Biomedical Resource Centre at UCL Institute of Ophthalmology and Moorfields; A.C.T. is a member of the International Diabetic Neuropathy Consortium, the Novo Nordisk Foundation (NNF14SA0006) and is a member of the DOLORisk consortium funded by the European Commission Horizon 2020 (ID633491); J. Whitworth is a recipient of a Cancer Research UK Cambridge Cancer Centre Clinical Research Training Fellowship; S.A.J. is funded by Kids Kidney Research; D.P.G. is funded by the MRC, Kidney Research UK and St Peters Trust for Kidney, Bladder and Prostate Research; The MPGN/DDD/C3 Glomerulopathy Rare Disease Group contributed to the recruitment and analysis for the PMG domain; K.J.M. is supported by the Northern Counties Kidney Research Fund; P.H.D. receives funding from ICP Support; T.K.B. received a PhD fellowship from the NHSBT and British Society of Haematology; H.S.M. receives support from BHF Programme Grant RG/16/4/32218; A.L. is a BHF Senior Basic Science Research Fellow - FS/13/48/30453; K.F. and C.V.-G. are supported by the Research Council of the University of Leuven (BOF KU Leuven‚ Belgium; OT/14/098); H.J.B. works for the Netherlands CardioVascular Research Initiative (CVON); Fiona Cunningham, Aoife McMahon, Glen Threadgold, and Joannella Morales received funding from the Wellcome Trust (grant numbers WT108749/Z/15/Z and WT200990/Z/16/Z) and the European Molecular Biology Laboratory. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care of England or any of the other funding agencies. Publisher Copyright: © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2020/7/2

Y1 - 2020/7/2

UR - http://www.scopus.com/inward/record.url?scp=85086777024&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85086777024&partnerID=8YFLogxK

U2 - 10.1038/s41586-020-2434-2

DO - 10.1038/s41586-020-2434-2

M3 - Article

C2 - 32581362

AN - SCOPUS:85086777024

SN - 0028-0836

VL - 583

SP - 96

EP - 102

JO - Nature

JF - Nature

IS - 7814

ER -

Whole-genome sequencing of patients with rare diseases in a national health system

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