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  • Cardiometabolic traits, sepsis and severe covid-19: a Mendelian randomization

    investigation

    Authors

    Mark J Ponsford, BMBCh MSc, Welsh Clinical Academic Trainee 1,2

    Apostolos Gkatzionis, MASt PhD, Career Development Fellow 3

    Venexia M Walker, PhD, Senior Research Associate 4,5

    Andrew J Grant, PhD, Research Associate 3

    Robyn E Wootton, PhD, Postdoctoral Researcher 4

    Luke S P Moore, FRCPath PhD, Consultant Infectious Diseases & Clinical Microbiology 6,7,8

    Segun Fatumo, PhD, Assistant Professor 9

    Amy M Mason, PhD, Research Associate 10,11

    Verena Zuber, PhD, Lecturer in Biostatistics 3,12

    Cristen Willer, PhD, Associate Professor 13

    Humaira Rasheed, PhD, Postdoctoral Researcher 4,14

    Ben Brumpton, PhD, Associate Professor 4,14,15

    Kristian Hveem, MD PhD, Professor 14

    Jan Kristian Damås, MD PhD, Professor 16,17

    Neil Davies, PhD, Senior Research Fellow 4,14

    Bjørn Olav Åsvold, MD PhD, Professor 14

    Erik Solligård, MD PhD, Professor 18

    Simon Jones, PhD, Professor 2

    Stephen Burgess, PhD, Statistician 3,10

    Tormod Rogne, MD PhD, Postdoctoral Researcher 18

    Dipender Gill, BMBCh PhD, Clinician Scientist 19

    . CC-BY-NC 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

    The copyright holder for this preprint this version posted June 20, 2020. ; https://doi.org/10.1101/2020.06.18.20134676doi: medRxiv preprint

    NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

    https://doi.org/10.1101/2020.06.18.20134676 http://creativecommons.org/licenses/by-nc/4.0/

  • Affiliations

    1 Immunodeficiency Centre or Wales, University Hospital Wales, Heath Park, Cardiff, UK.

    2 Division of Immunology, Infection, and Inflammation, Tenovus Institute, Cardiff University, Cardiff, UK.

    3 MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK.

    4 MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK.

    5 Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, USA.

    6 National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Imperial College London, UK.

    7 Chelsea & Westminster NHS Foundation Trust, London, UK.

    8 Imperial Biomedical Research Centre, Imperial College London and Imperial College NHS Healthcare Trust, London, UK.

    9 Department of Non-Communicable Diseases Epidemiology, London School of Hygiene & Tropical Medicine, UK.

    10 Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    11 National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge and Cambridge University Hospitals, Cambridge, UK

    12 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.

    13 Departments of Internal Medicine, Human Genetics and Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, USA.

    14 K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.

    15 Department of Thoracic Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

    16 Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.

    17 Department of Infectious Diseases, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

    18 Gemini Center for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, NTNU, Trondheim, Norway.

    19 Department of Epidemiology and Biostatistics, Medical School Building, St Mary's Hospital, Imperial College London, London, UK

    . CC-BY-NC 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

    The copyright holder for this preprint this version posted June 20, 2020. ; https://doi.org/10.1101/2020.06.18.20134676doi: medRxiv preprint

    https://doi.org/10.1101/2020.06.18.20134676 http://creativecommons.org/licenses/by-nc/4.0/

  • Address for correspondence Dr Dipender Gill Department of Epidemiology and Biostatistics, Medical School Building, St Mary's Hospital, Imperial College London, United Kingdom, W2 1PG Telephone: +44 (0) 7904843810 Email: [email protected] Author contributions DG, SB and MJP designed the project. VW, ND, BOA, ES and TR provided the data. TR, VW, AG1, SF and DG analysed the data. MJP, AG1, VW, AG2, SF, TR and DG drafted the manuscript. All authors interpreted the results and critically revised the manuscript for intellectual content. Competing interest statement All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare: LSPM has consulted for DNAelectronics (2015-18), Dairy Crest (2017–2018), bioMerieux (2013-20), Pfizer (2018-2020), and Umovis Lab (2020), received speaker fees from Profile Pharma (2018), received research grants from the National Institute for Health Research (2013-2020), CW+ Charity (2018-2019), and Leo Pharma (2016), and received educational grants from Eumedica (2016–2018). DG is employed part-time by Novo Nordisk. All other authors have no conflicts of interest to declare. Transparency declaration The corresponding authors affirm that the manuscript is an honest, accurate, and transparent account of the research being reported, and that no important aspects of the study have been omitted. Dissemination declaration This work uses genetic association summary data and dissemination to the participants that contributed these data is therefore not possible. Copyright The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non-exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd to permit this article (if accepted) to be published in BMJ editions and any other BMJPGL products and sublicences such use and exploit all subsidiary rights, as set out in our licence. Funding MJP is a funded by the Welsh Clinical Academic Training (WCAT) programme and is a participant in the NIH Graduate Partnership Program. AG1 is funded by a Medical Research Council Methodology Research Panel grant (RG88311). VW is supported by the Medical Research Council (MRC) Integrative Epidemiology Unit. The MRC and the University of Bristol support the MRC Integrative Epidemiology Unit [MC_UU_12013/1, MC_UU_12013/9, MC_UU_00011/1]. REW is supported by Wellcome Trust grant (204895/Z/16/Z). LSPM acknowledges the National Institute of Health Research (NIHR) Imperial Biomedical Research Centre (BRC) and the NIHR Health Protection Research Unit (HPRU) in Healthcare Associated Infection and Antimicrobial Resistance at Imperial College London in partnership with Public Health England. NMD is supported by a Norwegian Research Council Grant number 295989. SB and AG2 are supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (204623/Z/16/Z). DG is supported by the Wellcome 4i Program (203928/Z/16/Z) and British Heart Foundation Research Centre of Excellence (RE/18/4/34215) at Imperial College London. The funding sources did not have any role in designing the study, performing analysis or communicating findings.

    . CC-BY-NC 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

    The copyright holder for this preprint this version posted June 20, 2020. ; https://doi.org/10.1101/2020.06.18.20134676doi: medRxiv preprint

    https://doi.org/10.1101/2020.06.18.20134676 http://creativecommons.org/licenses/by-nc/4.0/

  • Acknowledgements This research was conducted using the UK Biobank Resource under Application Number 743915825. Quality Control filtering of the UK Biobank data was conducted by R. Mitchell, G. Hemani, T. Dudding, L. Corbin, S. Harrison, L. Paternoster as described in the published protocol (doi: 10.5523/bris.1ovaau5sxunp2cv8rcy88688v). The MRC IEU UK Biobank GWAS pipeline was developed by B. Elsworth, R. Mitchell, C. Raistrick, L. Paternoster, G. Hemani, T. Gaunt (doi: 10.5523/bris.pnoat8cxo0u52p6ynfaekeigi). The views expressed are those of the authors and not necessarily those of the National Health Service, National Institute for Health Research, or Department of Health and Social Care. The HUNT Study is a collaboration between the Nord-Trøndelag Health (HUNT) Research Centre (Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology), Nord-Trøndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. The genotyping in HUNT was financed by the National Institutes of Health; University of Michigan; the Research Council of Norway; the Liaison Committee for Education, Research and Innovat

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