- Record: found
- Abstract: found
- Article: found
Whole-genome sequencing reveals host factors underlying critical COVID-19
research-article
Author(s):
Athanasios Kousathanas
1 ,
Erola Pairo-Castineira
2
,
3 ,
Konrad Rawlik
2 ,
Alex Stuckey
1 ,
Christopher A. Odhams
1 ,
Susan Walker
1 ,
Clark D. Russell
2
,
4 ,
Tomas Malinauskas
5 ,
Yang Wu
6 ,
Jonathan Millar
2 ,
Xia Shen
7
,
8 ,
Katherine S. Elliott
5 ,
Fiona Griffiths
2 ,
Wilna Oosthuyzen
2 ,
Kirstie Morrice
9 ,
Sean Keating
10 ,
Bo Wang
2 ,
Daniel Rhodes
1 ,
Lucija Klaric
3 ,
Marie Zechner
2 ,
Nick Parkinson
2 ,
Afshan Siddiq
1 ,
Peter Goddard
1 ,
Sally Donovan
1 ,
David Maslove
11 ,
Alistair Nichol
12 ,
Malcolm G. Semple
13
,
14 ,
Tala Zainy
1 ,
Fiona Maleady-Crowe
1 ,
Linda Todd
1 ,
Shahla Salehi
1 ,
Julian Knight
5 ,
Greg Elgar
1 ,
Georgia Chan
1 ,
Prabhu Arumugam
1 ,
Christine Patch
1 ,
Augusto Rendon
1 ,
David Bentley
15 ,
Clare Kingsley
15 ,
Jack A. Kosmicki
16 ,
Julie E. Horowitz
16 ,
Aris Baras
16 ,
Goncalo R. Abecasis
16 ,
Manuel A. R. Ferreira
16 ,
Anne Justice
17 ,
Tooraj Mirshahi
17 ,
Matthew Oetjens
17 ,
Daniel J. Rader
18 ,
Marylyn D. Ritchie
18 ,
Anurag Verma
18 ,
Tom A. Fowler
1
,
19 ,
Manu Shankar-Hari
20 ,
Charlotte Summers
21 ,
Charles Hinds
22 ,
Peter Horby
23 ,
Lowell Ling
24 ,
Danny McAuley
25
,
26 ,
Hugh Montgomery
27 ,
Peter J. M. Openshaw
28
,
29 ,
Paul Elliott
30 ,
Timothy Walsh
10 ,
Albert Tenesa
2
,
3
,
8 ,
GenOMICC investigators,
23andMe investigators,
COVID-19 Human Genetics Initiative
Ebtehal Alsolm: dbaraka90@hotmail.com
,
Angie Fawkes
9 ,
Lee Murphy
9 ,
Kathy Rowan
31 ,
Chris P. Ponting
3 ,
Veronique Vitart
3 ,
James F. Wilson
3
,
8 ,
Jian Yang
32
,
33 ,
Andrew D. Bretherick
3 ,
Richard H. Scott
1
,
34 ,
Sara Clohisey Hendry
2 ,
Loukas Moutsianas
1 ,
Andy Law
2 ,
Mark J. Caulfield
1
,
35
,
,
J. Kenneth Baillie
2
,
3
,
4
,
10
,
Publication date (Electronic):
7 March 2022
Journal:
Nature
Publisher:
Nature Publishing Group UK
There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care 1 or hospitalization 2– 4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling ( IL10RB and PLSCR1), leucocyte differentiation ( BCL11A) and blood-type antigen secretor status ( FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase ( ATP11A), and increased expression of a mucin ( MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules ( SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.
Abstract
Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.
Related collections
Most cited references65
- Record: found
- Abstract: found
- Article: not found
KEGG: kyoto encyclopedia of genes and genomes.
M Kanehisa (2000)
KEGG (Kyoto Encyclopedia of Genes and Genomes) is a knowledge base for systematic analysis of gene functions, linking genomic information with higher order functional information. The genomic information is stored in the GENES database, which is a collection of gene catalogs for all the completely sequenced genomes and some partial genomes with up-to-date annotation of gene functions. The higher order functional information is stored in the PATHWAY database, which contains graphical representations of cellular processes, such as metabolism, membrane transport, signal transduction and cell cycle. The PATHWAY database is supplemented by a set of ortholog group tables for the information about conserved subpathways (pathway motifs), which are often encoded by positionally coupled genes on the chromosome and which are especially useful in predicting gene functions. A third database in KEGG is LIGAND for the information about chemical compounds, enzyme molecules and enzymatic reactions. KEGG provides Java graphics tools for browsing genome maps, comparing two genome maps and manipulating expression maps, as well as computational tools for sequence comparison, graph comparison and path computation. The KEGG databases are daily updated and made freely available (http://www. genome.ad.jp/kegg/).
- Record: found
- Abstract: found
- Article: not found
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis.
- Record: found
- Abstract: found
- Article: not found
Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report
Mark Peters (2021)
Abstract Background Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. Methods In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. Results A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). Conclusions In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)
Author and article information
Contributors
Mark J. Caulfield:
ORCID: http://orcid.org/0000-0001-9295-3594
m.j.caulfield@qmul.ac.uk
J. Kenneth Baillie:
ORCID: http://orcid.org/0000-0001-5258-793X
j.k.baillie@ed.ac.uk
Journal
Journal ID (nlm-ta): Nature
Journal ID (iso-abbrev): Nature
Title:
Nature
Publisher:
Nature Publishing Group UK
(London
)
ISSN
(Print):
0028-0836
ISSN
(Electronic):
1476-4687
Publication date
(Electronic):
7
March
2022
Publication date PMC-release: 7
March
2022
Publication date
(Print):
2022
Volume: 607
Issue: 7917
Pages: 97-103
Affiliations
[2
]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Roslin Institute, , University of Edinburgh, ; Edinburgh, UK
[3
]GRID grid.417068.c, ISNI 0000 0004 0624 9907, MRC Human Genetics Unit, Institute of Genetics and Cancer, , University of Edinburgh, Western General Hospital, ; Edinburgh, UK
[4
]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Centre for Inflammation Research, The Queen’s Medical Research Institute, , University of Edinburgh, ; Edinburgh, UK
[5
]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Wellcome Centre for Human Genetics, , University of Oxford, ; Oxford, UK
[6
]GRID grid.1003.2, ISNI 0000 0000 9320 7537, Institute for Molecular Bioscience, , The University of Queensland, ; Brisbane, Queensland Australia
[7
]GRID grid.8547.e, ISNI 0000 0001 0125 2443, Biostatistics Group, Greater Bay Area Institute of Precision Medicine (Guangzhou),
, Fudan University, ; Guangzhou, China
[8
]Centre for Global Health Research, Usher Institute of Population Health Sciences and
Informatics, Edinburgh, UK
[9
]GRID grid.417068.c, ISNI 0000 0004 0624 9907, Edinburgh Clinical Research Facility, , Western General Hospital, University of Edinburgh, ; Edinburgh, UK
[10
]GRID grid.418716.d, ISNI 0000 0001 0709 1919, Intensive Care Unit, , Royal Infirmary of Edinburgh, ; Edinburgh, UK
[11
]GRID grid.511274.4, Department of Critical Care Medicine, , Queen’s University and Kingston Health Sciences Centre, ; Kingston, Ontario Canada
[12
]GRID grid.7886.1, ISNI 0000 0001 0768 2743, Clinical Research Centre at St Vincent’s University Hospital, , University College Dublin, ; Dublin, Ireland
[13
]GRID grid.10025.36, ISNI 0000 0004 1936 8470, NIHR Health Protection Research Unit for Emerging and Zoonotic Infections, Institute
of Infection, Veterinary and Ecological Sciences, , University of Liverpool, ; Liverpool, UK
[14
]GRID grid.413582.9, ISNI 0000 0001 0503 2798, Respiratory Medicine and Institute in the Park, , Alder Hey Children’s Hospital and University of Liverpool, ; Liverpool, UK
[18
]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Department of Genetics, Perelman School of Medicine, , University of Pennsylvania, ; Philadelphia, PA USA
[19
]GRID grid.57981.32, Test and Trace, the Health Security Agency, Department of Health and Social Care,
; London, UK
[20
]GRID grid.420545.2, ISNI 0000 0004 0489 3985, Department of Intensive Care Medicine, , Guy’s and St Thomas’ NHS Foundation Trust, ; London, UK
[21
]GRID grid.5335.0, ISNI 0000000121885934, Department of Medicine, , University of Cambridge, ; Cambridge, UK
[22
]GRID grid.4868.2, ISNI 0000 0001 2171 1133, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry,
, Queen Mary University of London, ; London, UK
[23
]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, , University of Oxford, ; Oxford, UK
[24
]GRID grid.10784.3a, ISNI 0000 0004 1937 0482, Department of Anaesthesia and Intensive Care, , The Chinese University of Hong Kong, Prince of Wales Hospital, ; Hong Kong, China
[25
]GRID grid.4777.3, ISNI 0000 0004 0374 7521, Wellcome–Wolfson Institute for Experimental Medicine, , Queen’s University Belfast, ; Belfast, UK
[26
]GRID grid.416232.0, ISNI 0000 0004 0399 1866, Department of Intensive Care Medicine, , Royal Victoria Hospital, ; Belfast, UK
[27
]GRID grid.83440.3b, ISNI 0000000121901201, UCL Centre for Human Health and Performance, ; London, UK
[28
]GRID grid.7445.2, ISNI 0000 0001 2113 8111, National Heart and Lung Institute, , Imperial College London, ; London, UK
[29
]GRID grid.417895.6, ISNI 0000 0001 0693 2181, Imperial College Healthcare NHS Trust: London, ; London, UK
[31
]GRID grid.450885.4, ISNI 0000 0004 0381 1861, Intensive Care National Audit and Research Centre, ; London, UK
[32
]GRID grid.494629.4, ISNI 0000 0004 8008 9315, School of Life Sciences, , Westlake University, ; Hangzhou, China
[33
]GRID grid.494629.4, ISNI 0000 0004 8008 9315, Westlake Laboratory of Life Sciences and Biomedicine, ; Hangzhou, China
[35
]GRID grid.4868.2, ISNI 0000 0001 2171 1133, William Harvey Research Institute, , Queen Mary University of London, ; London, UK
[36
]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Roslin Institute, , University of Edinburgh, ; Edinburgh, UK
[37
]GRID grid.418716.d, ISNI 0000 0001 0709 1919, Intensive Care Unit, , Royal Infirmary of Edinburgh, ; Edinburgh, UK
[39
]GRID grid.4868.2, ISNI 0000 0001 2171 1133, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry,
, Queen Mary University of London, ; London, UK
[40
]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, , University of Oxford, ; Oxford, UK
[41
]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Wellcome Centre for Human Genetics, , University of Oxford, ; Oxford, UK
[43
]GRID grid.511274.4, Department of Critical Care Medicine, , Queen’s University and Kingston Health Sciences Centre, ; Kingston, Ontario Canada
[44
]GRID grid.4777.3, ISNI 0000 0004 0374 7521, Wellcome–Wolfson Institute for Experimental Medicine, , Queen’s University Belfast, ; Belfast, UK
[45
]GRID grid.416232.0, ISNI 0000 0004 0399 1866, Department of Intensive Care Medicine, , Royal Victoria Hospital, ; Belfast, UK
[46
]GRID grid.83440.3b, ISNI 0000000121901201, UCL Centre for Human Health and Performance, ; London, UK
[47
]GRID grid.7886.1, ISNI 0000 0001 0768 2743, Clinical Research Centre at St Vincent’s University Hospital, , University College Dublin, ; Dublin, Ireland
[48
]GRID grid.7445.2, ISNI 0000 0001 2113 8111, National Heart and Lung Institute, , Imperial College London, ; London, UK
[49
]GRID grid.417895.6, ISNI 0000 0001 0693 2181, Imperial College Healthcare NHS Trust: London, ; London, UK
[50
]GRID grid.11899.38, ISNI 0000 0004 1937 0722, Heart Institute, , University of São Paulo, ; São Paulo, Brazil
[51
]GRID grid.417068.c, ISNI 0000 0004 0624 9907, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, , University of Edinburgh, Western General Hospital, ; Edinburgh, UK
[52
]GRID grid.450885.4, ISNI 0000 0004 0381 1861, Intensive Care National Audit and Research Centre, ; London, UK
[53
]GRID grid.10025.36, ISNI 0000 0004 1936 8470, NIHR Health Protection Research Unit for Emerging and Zoonotic Infections, Institute
of Infection, Veterinary and Ecological Sciences, , University of Liverpool, ; Liverpool, UK
[54
]GRID grid.413582.9, ISNI 0000 0001 0503 2798, Respiratory Medicine and Institute in the Park, , Alder Hey Children’s Hospital and University of Liverpool, ; Liverpool, UK
[55
]GRID grid.420545.2, ISNI 0000 0004 0489 3985, Department of Intensive Care Medicine, , Guy’s and St Thomas’ NHS Foundation Trust, ; London, UK
[56
]GRID grid.5335.0, ISNI 0000000121885934, Department of Medicine, , University of Cambridge, ; Cambridge, UK
[57
]GRID grid.413629.b, ISNI 0000 0001 0705 4923, NIHR Clinical Research Network (CRN), , Hammersmith Hospital, ; London, UK
[58
]GRID grid.24029.3d, ISNI 0000 0004 0383 8386, Cambridge University Hospitals NHS Foundation Trust, ; Cambridge, UK
[59
]GRID grid.417068.c, ISNI 0000 0004 0624 9907, Edinburgh Clinical Research Facility, , Western General Hospital, University of Edinburgh, ; Edinburgh, UK
[60
]GRID grid.12981.33, ISNI 0000 0001 2360 039X, Biostatistics Group, State Key Laboratory of Biocontrol, School of Life Sciences,
, Sun Yat-sen University, ; Guangzhou, China
[61
]GRID grid.10419.3d, ISNI 0000000089452978, Department of Infectious Diseases, , Leiden University Medical Center, ; Leiden, The Netherlands
[64
]GRID grid.411812.f, ISNI 0000 0004 0400 2812, James Cook University Hospital, ; Middlesbrough, UK
[65
]GRID grid.439344.d, ISNI 0000 0004 0641 6760, Royal Stoke University Hospital, ; Stoke-on-Trent, UK
[66
]GRID grid.439355.d, ISNI 0000 0000 8813 6797, North Middlesex University Hospital NHS Trust, ; London, UK
[67
]GRID grid.439355.d, ISNI 0000 0000 8813 6797, North Middlesex University Hospital NHS Trust, ; London, UK
[68
]GRID grid.415970.e, ISNI 0000 0004 0417 2395, The Royal Liverpool University Hospital, ; Liverpool, UK
[70
]GRID grid.413820.c, ISNI 0000 0001 2191 5195, Charing Cross Hospital, St Mary’s Hospital and Hammersmith Hospital, ; London, UK
[86
]GRID grid.418395.2, ISNI 0000 0004 1756 4670, Royal Blackburn Teaching Hospital, ; Blackburn, UK
[87
]GRID grid.439712.a, ISNI 0000 0004 0398 7779, The Tunbridge Wells Hospital and Maidstone Hospital, ; Tunbridge Wells, UK
[90
]GRID grid.419297.0, ISNI 0000 0000 8487 8355, Royal Berkshire NHS Foundation Trust, ; Reading, UK
[92
]GRID grid.451090.9, ISNI 0000 0001 0642 1330, Northumbria Healthcare NHS Foundation Trust, ; North Shields, UK
[104
]GRID grid.413589.2, ISNI 0000 0004 0400 5650, The Alexandra Hospital, Redditch and Worcester Royal Hospital, ; Worcester, UK
[105
]GRID grid.415125.6, ISNI 0000 0004 0399 8830, Sandwell General Hospital and City Hospital, ; Birmingham, UK
[110
]GRID grid.443984.6, ISNI 0000 0000 8813 7132, St James’s University Hospital and Leeds General Infirmary, ; Leeds, UK
[117
]GRID grid.416885.6, ISNI 0000 0004 0417 5983, Tameside General Hospital, ; Ashton-under-Lyne, UK
[120
]GRID grid.419334.8, ISNI 0000 0004 0641 3236, Royal Victoria Infirmary, ; Newcastle-upon-Tyne, UK
[124
]GRID grid.416450.2, ISNI 0000 0004 0400 7971, North Manchester General Hospital, ; Manchester, UK
[130
]GRID grid.511123.5, ISNI 0000 0004 5988 7216, Queen Elizabeth University Hospital, ; Glasgow, UK
[133
]GRID grid.416391.8, ISNI 0000 0004 0400 0120, Norfolk and Norwich University Hospital (NNUH), ; Norwich, UK
[134
]GRID grid.415506.3, ISNI 0000 0004 0400 3364, Queen Elizabeth Hospital Gateshead, ; Gateshead, UK
[145
]GRID grid.416128.8, ISNI 0000 0000 9300 7922, Royal Hampshire County Hospital, ; Winchester, UK
[146
]GRID grid.451056.3, ISNI 0000 0001 2116 3923, Great Ormond St Hospital and UCL Great Ormond St Institute of Child Health NIHR Biomedical
Research Centre, ; London, UK
[149
]GRID grid.414262.7, ISNI 0000 0004 0400 7883, Basingstoke and North Hampshire Hospital, ; Basingstoke, UK
[151
]GRID grid.413868.0, ISNI 0000 0004 0417 2571, Chesterfield Royal Hospital Foundation Trust, ; Chesterfield, UK
[155
]GRID grid.416126.6, ISNI 0000 0004 0641 6031, Royal Hallamshire Hospital and Northern General Hospital, ; Sheffield, UK
[160
]GRID grid.415968.7, ISNI 0000 0004 0417 1480, Southport and Formby District General Hospital, ; Ormskirk, UK
[162
]GRID grid.417789.4, ISNI 0000 0004 0400 2687, Huddersfield Royal Infirmary, ; Huddersfield, UK
[167
]GRID grid.415251.6, ISNI 0000 0004 0400 9694, Princess Royal Hospital, Telford and Royal Shrewsbury Hospital, ; Shrewsbury, UK
[169
]GRID grid.416222.1, ISNI 0000 0004 0400 7007, Macclesfield District General Hospital, ; Macclesfield, UK
[172
]GRID grid.412910.f, ISNI 0000 0004 0641 6648, University Hospital of North Tees, ; Stockton-on-Tees, UK
[177
]GRID grid.413307.2, ISNI 0000 0004 0624 4030, University Hospital Crosshouse, ; Kilmarnock, UK
[183
]GRID grid.428062.a, ISNI 0000 0004 0497 2835, Chelsea and Westminster NHS Foundation Trust, ; London, UK
[200
]GRID grid.415545.4, ISNI 0000 0004 0398 7891, Queen Elizabeth the Queen Mother Hospital, ; Margate, UK
[203
]GRID grid.413704.5, ISNI 0000 0004 0399 9710, Eastbourne District General Hospital, ; Eastbourne, UK
[210
]GRID grid.412751.4, ISNI 0000 0001 0315 8143, University College Dublin, St Vincent’s University Hospital, ; Dublin, Ireland
[212
]GRID grid.413144.7, ISNI 0000 0001 0489 6543, Gloucestershire Royal Hospital, ; Gloucester, UK
[215
]GRID grid.415910.8, ISNI 0000 0001 0235 2382, Royal Manchester Children’s Hospital, ; Manchester, UK
[222
]GRID grid.15628.38, ISNI 0000 0004 0393 1193, University Hospitals Coventry and Warwickshire NHS Trust, ; Coventry, UK
[231
]GRID grid.415246.0, ISNI 0000 0004 0399 7272, Birmingham Children’s Hospital, ; Birmingham, UK
[232
]GRID grid.415992.2, ISNI 0000 0004 0398 7066, Liverpool Heart and Chest Hospital, ; Liverpool, UK
[235
]GRID grid.415183.a, ISNI 0000 0004 0400 3030, Furness General Hospital, ; Barrow-in-Furness, UK
[237
]GRID grid.412711.0, ISNI 0000 0004 0417 1042, Southend University Hospital, ; Westcliff-on-Sea, UK
[243
]GRID grid.411814.9, ISNI 0000 0004 0400 5511, James Paget University Hospital NHS Trust, ; Great Yarmouth, UK
[244
]GRID grid.412917.8, ISNI 0000 0004 0430 9259, The Christie NHS Foundation Trust, ; Manchester, UK
[246
]GRID grid.413525.4, ISNI 0000 0004 0624 4444, University Hospital Hairmyres, ; East Kilbride, UK
[247
]GRID grid.417148.f, ISNI 0000 0004 0649 0039, Withybush General Hospital, ; Haverfordwest, Wales UK
[252
]GRID grid.462305.6, ISNI 0000 0004 0408 8513, Harrogate and District NHS Foundation Trust, ; Harrogate, UK
[253
]GRID grid.436283.8, ISNI 0000 0004 0612 2631, National Hospital for Neurology and Neurosurgery, ; London, UK
[255
]GRID grid.413157.5, ISNI 0000 0004 0590 2070, Golden Jubilee National Hospital, ; Clydebank, UK
[256
]GRID grid.439591.3, ISNI 0000 0004 0399 2770, Homerton University Hospital Foundation NHS Trust, ; London, UK
[258
]GRID grid.416080.b, ISNI 0000 0004 0400 9774, The Royal Alexandra Children’s Hospital, ; Brighton, UK
[260
]GRID grid.418236.a, ISNI 0000 0001 2162 0389, Human Genetics R&D and Target Sciences R&D, , GSK Medicines Research Centre, ; Stevenage, UK
[262
]GRID grid.7737.4, ISNI 0000 0004 0410 2071, Institute for Molecular Medicine Finland (FIMM), , University of Helsinki, ; Helsinki, Finland
[263
]GRID grid.66859.34, ISNI 0000 0004 0546 1623, Broad Institute of MIT and Harvard, ; Cambridge, MA USA
[264
]GRID grid.59734.3c, ISNI 0000 0001 0670 2351, Icahn School of Medicine at Mount Sinai, ; New York, NY USA
[266
]GRID grid.48324.39, ISNI 0000000122482838, Centre for Bioinformatics and Data Analysis, , Medical University of Bialystok, ; Bialystok, Poland
[267
]GRID grid.417068.c, ISNI 0000 0004 0624 9907, Institute of Genetics and Cancer, , University of Edinburgh, Western General Hospital, ; Edinburgh, UK
[269
]GRID grid.239552.a, ISNI 0000 0001 0680 8770, Center for Applied Genomics, , Children’s Hospital of Philadelphia, ; Philadelphia, PA USA
[270
]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Department of Pediatrics, Perelman School of Medicine, , University of Pennsylvania, ; Philadelphia, PA USA
[271
]GRID grid.412807.8, ISNI 0000 0004 1936 9916, Vanderbilt University Medical Center, ; Nashville, TN USA
[272
]GRID grid.10698.36, ISNI 0000000122483208, University of North Carolina at Chapel Hill, ; Chapel Hill, NC USA
[273
]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Roslin Institute, The Royal (Dick) School of Veterinary Studies, , University of Edinburgh, ; Edinburgh, UK
[274
]GRID grid.32224.35, ISNI 0000 0004 0386 9924, Analytic and Translational Genetics Unit, , Massachusetts General Hospital, ; Boston, MA USA
[275
]Genolier Innovation Network and Hub, Swiss Medical Network, Genolier Healthcare Campus,
Genolier, Switzerland
[276
]GRID grid.10251.37, ISNI 0000000103426662, Department of Pediatrics, Faculty of Medicine, , Mansoura University, ; Mansoura, Egypt
[277
]GRID grid.412258.8, ISNI 0000 0000 9477 7793, Department of Clinical Pathology, Faculty of Medicine, , Tanta University, ; Tanta, Egypt
[278
]GRID grid.10251.37, ISNI 0000000103426662, Department of Anaethesia and Critical Care, Faculty of Medicine, , Mansoura University, ; Mansoura, Egypt
[279
]GRID grid.10251.37, ISNI 0000000103426662, Department of Surgery, Faculty of Medicine, , Mansoura University, ; Mansoura, Egypt
[280
]GRID grid.412258.8, ISNI 0000 0000 9477 7793, Department of Internal Medicine, Faculty of Medicine, , Tanta University, ; Tanta, Egypt
[281
]GRID grid.412258.8, ISNI 0000 0000 9477 7793, Faculty of Science, , Tanta University, ; Tanta, Egypt
[282
]GRID grid.412258.8, ISNI 0000 0000 9477 7793, Chest Department, Faculty of Medicine, , Tanta University, ; Tanta, Egypt
[283
]GRID grid.10251.37, ISNI 0000000103426662, Department of Clinical Pathology, Faculty of Medicine, , Mansoura University, ; Mansoura, Egypt
[284
]GRID grid.12361.37, ISNI 0000 0001 0727 0669, Department of Biosciences, School of Science and Technology, , Nottingham Trent University, ; Nottingham, UK
[285
]GRID grid.10251.37, ISNI 0000000103426662, Chest Department, Faculty of Medicine, , Mansoura University, ; Mansoura, Egypt
[286
]GRID grid.412258.8, ISNI 0000 0000 9477 7793, Anesthesia, Surgical Intensive Care and Pain Management Department, Faculty of Medicine,
, Tanta University, ; Tanta, Egypt
[287
]GRID grid.10251.37, ISNI 0000000103426662, Department of Medical Biochemistry, Faculty of Medicine, , Mansoura University, ; Mansoura, Egypt
[288
]GRID grid.10251.37, ISNI 0000000103426662, Department of Tropical Medicine, Faculty of Medicine, , Mansoura University, ; Mansoura, Egypt
[290
]GRID grid.412258.8, ISNI 0000 0000 9477 7793, Pediatrics Department, Faculty of Medicine, , Tanta University, ; Tanta, Egypt
[291
]GRID grid.9918.9, ISNI 0000 0004 1936 8411, Department of Health Sciences, , University of Leicester, ; Leicester, UK
[293
]GRID grid.9918.9, ISNI 0000 0004 1936 8411, Department of Respiratory Sciences, , University of Leicester, ; Leicester, UK
[295
]GRID grid.415646.4, ISNI 0000 0004 0612 6034, Digestive Oncology Research Center, Digestive Disease Research Institute, , Shariati Hospital, Tehran University of Medical Sciences, ; Tehran, Iran
[296
]GRID grid.415646.4, ISNI 0000 0004 0612 6034, Department of Pulmonology, School of Medicine, , Shariati Hospital, Tehran University of Medical Sciences, ; Tehran, Iran
[298
]GRID grid.415646.4, ISNI 0000 0004 0612 6034, Department of Emergency Intensive Care Unit, School of Medicine, , Shariati Hospital, Tehran University of Medical Sciences, ; Tehran, Iran
[299
]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Department of Anesthesiology, School of Medicine, , Amir Alam Hospital, Tehran University of Medical Sciences, ; Tehran, Iran
[300
]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Department of Pulmonology, School of Medicine, , Tehran University of Medical Sciences, ; Tehran, Iran
[302
]GRID grid.419140.9, ISNI 0000 0001 0690 0331, Department of Microbiology, Health and Family Research Center, , NIOC Hospital, ; Tehran, Iran
[303
]GRID grid.415646.4, ISNI 0000 0004 0612 6034, Department of Emergency Medicine, School of Medicine, , Shariati Hospital, Tehran University of Medical Sciences, ; Tehran, Iran
[304
]GRID grid.411705.6, ISNI 0000 0001 0166 0922, Department of Anesthesiology, School of Medicine, , Tehran University of Medical Sciences, ; Tehran, Iran
[305
]GRID grid.411463.5, ISNI 0000 0001 0706 2472, Department of Pathology, Faculty of Medicine, , Tehran Azad University, ; Tehran, Iran
[306
]GRID grid.7922.e, ISNI 0000 0001 0244 7875, Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Faculty of Medicine,
, Chulalongkorn University, ; Bangkok, Thailand
[307
]GRID grid.7922.e, ISNI 0000 0001 0244 7875, Department of Pharmacology, Faculty of Medicine, , Chulalongkorn University, ; Bangkok, Thailand
[308
]GRID grid.412739.a, ISNI 0000 0000 9006 7188, Department of Pathology, Faculty of Medicine, Nakornnayok, , Srinakharinwirot University, ; Bangkok, Thailand
[309
]GRID grid.7922.e, ISNI 0000 0001 0244 7875, Center of Excellence for Medical Genomics, Medical Genomics Cluster, Faculty of Medicine,
, Chulalongkorn University, ; Bangkok, Thailand
[310
]Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial
Hospital, The Thai Red Cross Society, Bangkok, Thailand
[311
]GRID grid.7922.e, ISNI 0000 0001 0244 7875, Department of Mathematics and Computer Science, Faculty of Science, , Chulalongkorn University, ; Bangkok, Thailand
[312
]GRID grid.7922.e, ISNI 0000 0001 0244 7875, Omics Sciences and Bioinfomatics Center, Faculty of Science, , Chulalongkorn University, ; Bangkok, Thailand
[313
]GRID grid.7922.e, ISNI 0000 0001 0244 7875, Research Affairs, Faculty of Medicine, , Chulalongkorn University, ; Bangkok, Thailand
[314
]GRID grid.411628.8, ISNI 0000 0000 9758 8584, Thai Red Cross Emerging Infectious Diseases Clinical Centre, , King Chulalongkorn Memorial Hospital, ; Bangkok, Thailand
[315
]GRID grid.7922.e, ISNI 0000 0001 0244 7875, Department of Pediatrics, Faculty of Medicine, , Chulalongkorn University, ; Bangkok, Thailand
[316
]GRID grid.7922.e, ISNI 0000 0001 0244 7875, Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, , Chulalongkorn University, ; Bangkok, Thailand
[317
]GRID grid.7922.e, ISNI 0000 0001 0244 7875, Center of Excellence in Pediatric Infectious Diseases and Vaccines, , Chulalongkorn University, ; Bangkok, Thailand
[318
]GRID grid.7922.e, ISNI 0000 0001 0244 7875, Department of Microbiology, Faculty of Medicine, , Chulalongkorn University, ; Bangkok, Thailand
[319
]GRID grid.7922.e, ISNI 0000 0001 0244 7875, Immunology Division, Department of Microbiology, Faculty of Medicine, , Chulalongkorn University, ; Bangkok, Thailand
[320
]GRID grid.7922.e, ISNI 0000 0001 0244 7875, Center of Excellence in Immunology and Immune-mediated Diseases, Department of Microbiology,
Faculty of Medicine, , Chulalongkorn University, ; Bangkok, Thailand
[321
]GRID grid.7922.e, ISNI 0000 0001 0244 7875, Healthcare-associated Infection Research Group STAR (Special Task Force for Activating
Research), , Chulalongkorn University, ; Bangkok, Thailand
[322
]GRID grid.5947.f, ISNI 0000 0001 1516 2393, K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing,
, Norwegian University of Science and Technology (NTNU), ; Trondheim, Norway
[323
]GRID grid.5947.f, ISNI 0000 0001 1516 2393, HUNT Research Center, Department of Public Health and Nursing, , Norwegian University of Science and Technology (NTNU), ; Levanger, Norway
[324
]GRID grid.52522.32, ISNI 0000 0004 0627 3560, Clinic of Medicine, , St Olav’s Hospital, Trondheim University Hospital, ; Trondheim, Norway
[325
]GRID grid.214458.e, ISNI 0000000086837370, Division of Cardiovascular Medicine, Department of Internal Medicine, , University of Michigan, ; Ann Arbor, MI USA
[326
]GRID grid.214458.e, ISNI 0000000086837370, Department of Computational Medicine and Bioinformatics, , University of Michigan, ; Ann Arbor, MI USA
[327
]GRID grid.66859.34, ISNI 0000 0004 0546 1623, Program in Medical and Population Genetics, , Broad Institute of Harvard and MIT, ; Cambridge, MA USA
[328
]GRID grid.5947.f, ISNI 0000 0001 1516 2393, Gemini Center for Sepsis Research, Department of Circulation and Medical Imaging,
, Norwegian University of Science and Technology (NTNU), ; Trondheim, Norway
[329
]GRID grid.47100.32, ISNI 0000000419368710, Department of Chronic Disease Epidemiology and Center for Perinatal, Pediatric and
Environmental Epidemiology, , Yale School of Public Health, ; New Haven, CT USA
[330
]GRID grid.52522.32, ISNI 0000 0004 0627 3560, Clinic of Anaesthesia and Intensive Care, , St Olav’s Hospital, Trondheim University Hospital, ; Trondheim, Norway
[331
]GRID grid.452562.2, ISNI 0000 0000 8808 6435, Genomics Research Department, Saudi Human Genome Project, , King Fahad Medical City and King Abdulaziz City for Science and Technology (KACST),
; Riyadh, Saudi Arabia
[332
]GRID grid.412149.b, ISNI 0000 0004 0608 0662, Developmental Medicine Department, , King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University
for Health Sciences, Ministry of National Guard Health Affairs, ; Riyadh, Saudi Arabia
[333
]GRID grid.452562.2, ISNI 0000 0000 8808 6435, Saudi Human Genome Project (SHGP), , King Abdulaziz City for Science and Technology (KACST), Satellite Lab at King Abdulaziz
Medical City, Ministry of National Guard Health Affairs, ; Riyadh, Saudi Arabia
[334
]GRID grid.415310.2, ISNI 0000 0001 2191 4301, The Liver Transplant Unit, , King Faisal Specialist Hospital and Research Centre, ; Riyadh, Saudi Arabia
[335
]GRID grid.21107.35, ISNI 0000 0001 2171 9311, The Division of Gastroenterology and Hepatology, , Johns Hopkins University, ; Baltimore, MD USA
[336
]GRID grid.56302.32, ISNI 0000 0004 1773 5396, Department of Pathology, College of Medicine, , King Saud University, ; Riyadh, Saudi Arabia
[337
]GRID grid.42505.36, ISNI 0000 0001 2156 6853, Titus Family Department of Clinical Pharmacy, USC School of Pharmacy, , University of Southern California, ; Los Angeles, CA USA
[338
]GRID grid.412892.4, ISNI 0000 0004 1754 9358, College of Applied Medical Sciences, , Taibah University, ; Madina, Saudi Arabia
[339
]GRID grid.412149.b, ISNI 0000 0004 0608 0662, Developmental Medicine Department, , King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University
for Health Sciences, Ministry of National Guard Health Affairs, ; Riyadh, Saudi Arabia
[340
]GRID grid.452562.2, ISNI 0000 0000 8808 6435, KACST-BWH Centre of Excellence for Biomedicine, Joint Centers of Excellence Program,
, King Abdulaziz City for Science and Technology (KACST), ; Riyadh, Saudi Arabia
[341
]GRID grid.412149.b, ISNI 0000 0004 0608 0662, Ministry of the National Guard Health Affairs, , King Abdullah International Medical Research Center and King Saud Bin Abdulaziz University
for Health Sciences, ; Riyadh, Saudi Arabia
[342
]GRID grid.415696.9, ISNI 0000 0004 0573 9824, Ohud Hospital, Ministry of Health, ; Madinah, Saudi Arabia
[343
]GRID grid.415277.2, ISNI 0000 0004 0593 1832, Pediatric Infectious Diseases, , Children’s Specialized Hospital, King Fahad Medical City, ; Riyadh, Saudi Arabia
[344
]GRID grid.412149.b, ISNI 0000 0004 0608 0662, The Saudi Biobank, King Abdullah International Medical Research Center, , King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard
Health Affairs, ; Riyadh, Saudi Arabia
[345
]GRID grid.415254.3, ISNI 0000 0004 1790 7311, Developmental Medicine Department, , King Abdullah International Medical Research Center and King Saud Bin Abdulaziz University
for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health
Affairs, ; Riyadh, Saudi Arabia
[346
]GRID grid.415254.3, ISNI 0000 0004 1790 7311, Department of Pathology and Laboratory Medicine, , King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Saud
Bin Abdulaziz University for Health Sciences and King Abdullah International Medical
Research Center, ; Riyadh, Saudi Arabia
[347
]GRID grid.415462.0, ISNI 0000 0004 0607 3614, Laboratory Department, , Security Forces Hospital, General Directorate of Medical Services, Ministry of Interior,
; Riyadh, Saudi Arabia
[348
]GRID grid.56302.32, ISNI 0000 0004 1773 5396, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, , King Saud University, ; Riyadh, Saudi Arabia
[349
]GRID grid.452562.2, ISNI 0000 0000 8808 6435, King Abdulaziz City for Science and Technology (KACST), ; Riyadh, Saudi Arabia
[350
]GRID grid.452562.2, ISNI 0000 0000 8808 6435, Life Science and Environmental Institute, , King Abdulaziz City for Science and Technology (KACST), ; Riyadh, Saudi Arabia
[351
]GRID grid.412149.b, ISNI 0000 0004 0608 0662, Department of Developmental Medicine, King Abdullah International Medical Research
Center, , King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City,
Ministry of National Guard Health Affairs, ; Riyadh, Saudi Arabia
[352
]GRID grid.42505.36, ISNI 0000 0001 2156 6853, Titus Family Department of Clinical Pharmacy, , USC School of Pharmacy University of Southern California, ; Los Angeles, CA USA
[353
]GRID grid.418193.6, ISNI 0000 0001 1541 4204, Centre for Fertility and Health, , Norwegian Institute of Public Health, ; Oslo, Norway
[354
]GRID grid.418193.6, ISNI 0000 0001 1541 4204, Department of Method Development and Analytics, , Norwegian Institute of Public Health, ; Oslo, Norway
[355
]GRID grid.418193.6, ISNI 0000 0001 1541 4204, Department of Genetics and Bioinformatics, , Norwegian Institute of Public Health, ; Oslo, Norway
[356
]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Department of Twin Research and Genetic Epidemiology, , King’s College London, ; London, UK
[357
]GRID grid.420545.2, ISNI 0000 0004 0489 3985, NIHR Biomedical Research Centre at Guy’s and St Thomas’ Foundation Trust, ; London, UK
[359
]GRID grid.413396.a, ISNI 0000 0004 1768 8905, Stroke Pharmacogenomics and Genetics, , Biomedical Research Institute Sant Pau, Sant Pau Hospital, ; Barcelona, Spain
[360
]GRID grid.4711.3, ISNI 0000 0001 2183 4846, Institute of Biomedicine of Valencia (IBV), National Spanish Research Council (CSIC),
; València, Spain
[361
]Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), València,
Spain
[363
]GRID grid.4711.3, ISNI 0000 0001 2183 4846, Institute for Biomedical Research of Barcelona (IIBB), , National Spanish Research Council (CSIC), ; Barcelona, Spain
[364
]GRID grid.414875.b, ISNI 0000 0004 1794 4956, Department of Neurology, , Hospital Universitari MútuaTerrassa, Fundació Docència i Recerca MútuaTerrassa, ; Terrassa, Spain
[365
]GRID grid.5515.4, ISNI 0000000119578126, Department of Molecular and Cell Biology, , Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid,
; Madrid, Spain
[366
]GRID grid.469953.4, ISNI 0000 0004 1757 2371, Instituto de Física de Cantabria (IFCA-CSIC), ; Santander, Spain
[367
]GRID grid.10403.36, ISNI 0000000091771775, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), ; Barcelona, Spain
[369
]GRID grid.5841.8, ISNI 0000 0004 1937 0247, Hospital Clínic, IDIBAPS, School of Medicine, , University of Barcelona, ; Barcelona, Spain
[375
]GRID grid.5239.d, ISNI 0000 0001 2286 5329, Instituto de Biomedicina y Genética Molecular (IBGM), CSIC-Universidad de Valladolid,
; Valladolid, Spain
[376
]GRID grid.411057.6, ISNI 0000 0000 9274 367X, Hospital Clínico Universitario de Valladolid (SACYL), ; Valladolid, Spain
[378
]GRID grid.413396.a, ISNI 0000 0004 1768 8905, Department of Neurology, , Biomedical Research Institute Sant Pau (IIB Sant Pau), Hospital de la Santa Creu i
Sant Pau, ; Barcelona, Spain
[379
]GRID grid.411347.4, ISNI 0000 0000 9248 5770, Hospital Universitario Ramon y Cajal, IRYCIS, ; Madrid, Spain
[380
]GRID grid.411109.c, ISNI 0000 0000 9542 1158, Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío,
CSIC and University of Seville, ; Seville, Spain
[381
]GRID grid.411375.5, ISNI 0000 0004 1768 164X, Department of Neurology, , Hospital Universitario Virgen Macarena, ; Seville, Spain
[384
]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Division of Human Genetics, Department of Pediatrics, The Perelman School of Medicine,
, University of Pennsylvania, ; Philadelphia, PA USA
[385
]GRID grid.14013.37, ISNI 0000 0004 0640 0021, Faculty of Medicine, , University of Iceland, ; Reykjavik, Iceland
[387
]GRID grid.14758.3f, ISNI 0000 0001 1013 0499, Finnish Institute for Health and Welfare (THL), ; Helsinki, Finland
[388
]GRID grid.7737.4, ISNI 0000 0004 0410 2071, University of Helsinki, Faculty of Medicine, Clinical and Molecular Metabolism Research
Program, ; Helsinki, Finland
[389
]GRID grid.7737.4, ISNI 0000 0004 0410 2071, Public Health, Faculty of Medicine, , University of Helsinki, ; Helsinki, Finland
[390
]GRID grid.14709.3b, ISNI 0000 0004 1936 8649, Department of Human Genetics, , McGill University, ; Montréal, Québec Canada
[391
]GRID grid.414980.0, ISNI 0000 0000 9401 2774, Lady Davis Institute, , Jewish General Hospital, McGill University, ; Montréal, Québec Canada
[392
]GRID grid.258799.8, ISNI 0000 0004 0372 2033, Kyoto–McGill International Collaborative School in Genomic Medicine, Graduate School
of Medicine, , Kyoto University, ; Kyoto, Japan
[393
]GRID grid.54432.34, ISNI 0000 0001 0860 6072, Research Fellow, Japan Society for the Promotion of Science, ; Kyoto, Japan
[396
]GRID grid.411374.4, ISNI 0000 0000 8607 6858, 5BHUL (Liege Biobank), , CHU of Liege, ; Liege, Belgium
[398
]GRID grid.430503.1, ISNI 0000 0001 0703 675X, University of Colorado Anschutz Medical Campus, ; Aurora, CO USA
[399
]GRID grid.10939.32, ISNI 0000 0001 0943 7661, Estonian Genome Centre, , Institute of Genomics, University of Tartu, ; Tartu, Estonia
[403
]GRID grid.10939.32, ISNI 0000 0001 0943 7661, Institute of Biomedicine and Translational Medicine, , University of Tartu, ; Tartu, Estonia
[406
]GRID grid.9851.5, ISNI 0000 0001 2165 4204, Infectious Diseases Service, Department of Medicine, , University Hospital and University of Lausanne, ; Lausanne, Switzerland
[407
]GRID grid.508836.0, Institute of Molecular and Clinical Ophthalmology Basel (IOB), ; Basel, Switzerland
[408
]GRID grid.6612.3, ISNI 0000 0004 1937 0642, Department of Ophthalmology, , University of Basel, ; Basel, Switzerland
[409
]GRID grid.9851.5, ISNI 0000 0001 2165 4204, Centre for Primary Care and Public Health, , University of Lausanne, ; Lausanne, Switzerland
[410
]GRID grid.413349.8, ISNI 0000 0001 2294 4705, Division of Infectious Diseases and Hospital Epidemiology, , Cantonal Hospital St Gallen, ; St Gallen, Switzerland
[411
]GRID grid.8591.5, ISNI 0000 0001 2322 4988, Division of Intensive Care, , Geneva University Hospitals and the University of Geneva Faculty of Medicine, ; Geneva, Switzerland
[412
]GRID grid.150338.c, ISNI 0000 0001 0721 9812, Infectious Disease Service, Department of Internal Medicine, , Geneva University Hospital, ; Geneva, Switzerland
[414
]Infectious Diseases Division, University Hospital Centre of the canton of Vaud, Hospital
of Valais, Sion, Switzerland
[415
]GRID grid.429186.0, ISNI 0000 0004 1756 6852, GCAT-Genomes for Life, , Germans Trias i Pujol Health Sciences Research Institute (IGTP), ; Badalona, Spain
[416
]GRID grid.418284.3, ISNI 0000 0004 0427 2257, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, , Consortium for Biomedical Research in Epidemiology and Public Health and University
of Barcelona, ; Barcelona, Spain
[417
]GRID grid.32224.35, ISNI 0000 0004 0386 9924, Massachusetts General Hospital, ; Boston, MA USA
[418
]GRID grid.10097.3f, ISNI 0000 0004 0387 1602, Life and Medical Sciences, , Barcelona Supercomputing Center–Centro Nacional de Supercomputación (BSC-CNS), ; Barcelona, Spain
[420
]GRID grid.411142.3, ISNI 0000 0004 1767 8811, IMIM (Hospital del Mar Medical Research Institute), ; Barcelona, Spain
[421
]GRID grid.5612.0, ISNI 0000 0001 2172 2676, Universitat Pompeu Fabra (UPF), ; Barcelona, Spain
[422
]GRID grid.466571.7, ISNI 0000 0004 1756 6246, CIBER Epidemiología y Salud Pública (CIBERESP), ; Madrid, Spain
[423
]GRID grid.9024.f, ISNI 0000 0004 1757 4641, Medical Genetics, , University of Siena, ; Siena, Italy
[424
]GRID grid.411477.0, ISNI 0000 0004 1759 0844, Genetica Medica, , Azienda Ospedaliero-Universitaria Senese, ; Siena, Italy
[425
]GRID grid.9024.f, ISNI 0000 0004 1757 4641, Med Biotech Hub and Competence Center, Department of Medical Biotechnologies, , University of Siena, ; Siena, Italy
[426
]GRID grid.417287.f, ISNI 0000 0004 1760 3158, Infectious Diseases Clinic, Department of Medicine 2, , Azienda Ospedaliera di Perugia and University of Perugia, Santa Maria Hospital, ; Perugia, Italy
[427
]GRID grid.7548.e, ISNI 0000000121697570, Department of Anesthesia and Intensive Care, , University of Modena and Reggio Emilia, ; Modena, Italy
[428
]GRID grid.419425.f, ISNI 0000 0004 1760 3027, Division of Infectious Diseases and Immunology, , Fondazione IRCCS Policlinico San Matteo, ; Pavia, Italy
[429
]GRID grid.8982.b, ISNI 0000 0004 1762 5736, Department of Internal Medicine and Therapeutics, , University of Pavia, ; Pavia, Italy
[430
]GRID grid.414266.3, ISNI 0000 0004 1759 8539, U.O.C. Medicina, ASST Nord Milano, , Ospedale Bassini, ; Milan, Italy
[431
]GRID grid.8982.b, ISNI 0000 0004 1762 5736, Department of Mathematics, , University of Pavia, ; Pavia, Italy
[434
]GRID grid.414818.0, ISNI 0000 0004 1757 8749, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, ; Milan, Italy
[435
]GRID grid.7637.5, ISNI 0000000417571846, Department of Infectious and Tropical Diseases, , University of Brescia and ASST Spedali Civili Hospital, ; Brescia, Italy
[436
]GRID grid.7637.5, ISNI 0000000417571846, Department of Molecular and Translational Medicine, , University of Brescia, ; Brescia, Italy
[437
]GRID grid.412725.7, Clinical Chemistry Laboratory, Cytogenetics and Molecular Genetics Section, Diagnostic
Department, , ASST Spedali Civili di Brescia, ; Brescia, Italy
[438
]GRID grid.416292.a, ISNI 0000 0004 1759 8897, Chirurgia Vascolare, , Ospedale Maggiore di Crema, ; Crema, Italy
[440
]GRID grid.4708.b, ISNI 0000 0004 1757 2822, Department of Biomedical and Clinical Sciences Luigi Sacco, , University of Milan, ; Milan, Italy
[441
]GRID grid.411477.0, ISNI 0000 0004 1759 0844, Department of Specialized and Internal Medicine, Tropical and Infectious Diseases
Unit, , Azienda Ospedaliera Universitaria Senese, ; Siena, Italy
[442
]GRID grid.419423.9, ISNI 0000 0004 1760 4142, HIV/AIDS Department, , National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, ; Rome, Italy
[443
]GRID grid.9024.f, ISNI 0000 0004 1757 4641, Unit of Respiratory Diseases and Lung Transplantation, Department of Internal and
Specialist Medicine, , University of Siena, ; Siena, Italy
[444
]GRID grid.411477.0, ISNI 0000 0004 1759 0844, Unit of Intensive Care Medicine. Departments of Emergency and Urgency, Medicine, Surgery
and Neurosciences, , Siena University Hospital, ; Siena, Italy
[445
]GRID grid.9024.f, ISNI 0000 0004 1757 4641, Unit of Diagnostic Imaging, Departments of Medical, Surgical and Neurosciences and
Radiological Sciences, , University of Siena, ; Siena, Italy
[446
]GRID grid.9024.f, ISNI 0000 0004 1757 4641, Rheumatology Unit, Department of Medicine, Surgery and Neurosciences, , University of Siena, Policlinico Le Scotte, ; Siena, Italy
[447
]GRID grid.416351.4, ISNI 0000 0004 1789 6237, Infectious Diseases Unit, Department of Specialized and Internal Medicine, , San Donato Hospital Arezzo, ; Arezzo, Italy
[448
]GRID grid.416351.4, ISNI 0000 0004 1789 6237, Anesthesia Unit, Department of Emergency, , San Donato Hospital, ; Arezzo, Italy
[449
]GRID grid.416351.4, ISNI 0000 0004 1789 6237, Pneumology Unit and UTIP, Department of Specialized and Internal Medicine, , San Donato Hospital, ; Arezzo, Italy
[450
]GRID grid.415928.3, Anesthesia Unit, Department of Emergency, , Misericordia Hospital, ; Grosseto, Italy
[451
]GRID grid.415928.3, Infectious Diseases Unit, Department of Specialized and Internal Medicine, , Misericordia Hospital, ; Grosseto, Italy
[453
]GRID grid.415928.3, Clinical Chemical Analysis Laboratory, , Misericordia Hospital, ; Grosseto, Italy
[455
]GRID grid.416351.4, ISNI 0000 0004 1789 6237, Clinical Chemical Analysis Laboratory, , San Donato Hospital, ; Arezzo, Italy
[456
]GRID grid.4708.b, ISNI 0000 0004 1757 2822, Department of Health Sciences, Clinic of Infectious Diseases, ASST Santi Paolo e Carlo,
, University of Milan, ; Milan, Italy
[457
]GRID grid.7548.e, ISNI 0000000121697570, Department of Medical and Surgical Sciences for Children and Adults, , University of Modena and Reggio Emilia, ; Modena, Italy
[458
]GRID grid.9027.c, ISNI 0000 0004 1757 3630, Infectious Diseases Clinic, , Santa Maria Hospital, University of Perugia, ; Perugia, Italy
[462
]GRID grid.5608.b, ISNI 0000 0004 1757 3470, Department of Molecular Medicine, , University of Padova, ; Padua, Italy
[463
]GRID grid.413172.2, Medical Genetics and Laboratory of Medical Genetics Unit, , A.O.R.N. Antonio Cardarelli Hospital, ; Naples, Italy
[464
]GRID grid.4691.a, ISNI 0000 0001 0790 385X, Department of Molecular Medicine and Medical Biotechnology, , University of Naples Federico II, ; Naples, Italy
[467
]GRID grid.416052.4, ISNI 0000 0004 1755 4122, Unit of Respiratory Physiopathology, , AORN dei Colli, Monaldi Hospital, ; Naples, Italy
[468
]GRID grid.413503.0, ISNI 0000 0004 1757 9135, Division of Medical Genetics, , Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, ; San Giovanni Rotondo, Italy
[469
]GRID grid.413503.0, ISNI 0000 0004 1757 9135, Laboratory of Regulatory and Functional Genomics, , Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, ; San Giovanni Rotondo, Italy
[470
]GRID grid.413503.0, ISNI 0000 0004 1757 9135, Department of Medical Sciences, , Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, ; San Giovanni Rotondo, Italy
[471
]GRID grid.413503.0, ISNI 0000 0004 1757 9135, Clinical Trial Office, , Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, ; San Giovanni Rotondo, Italy
[472
]GRID grid.5606.5, ISNI 0000 0001 2151 3065, Department of Health Sciences, , University of Genova, ; Genova, Italy
[473
]GRID grid.410345.7, ISNI 0000 0004 1756 7871, Infectious Diseases Clinic, , Policlinico San Martino Hospital, IRCCS for Cancer Research, ; Genova, Italy
[474
]GRID grid.411075.6, ISNI 0000 0004 1760 4193, Microbiology, , Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Catholic University of
Medicine, ; Rome, Italy
[475
]GRID grid.414603.4, Department of Laboratory Sciences and Infectious Diseases, , Fondazione Policlinico Universitario A. Gemelli IRCCS, ; Rome, Italy
[476
]GRID grid.9024.f, ISNI 0000 0004 1757 4641, Department of Cardiovascular Diseases, , University of Siena, ; Siena, Italy
[477
]GRID grid.9024.f, ISNI 0000 0004 1757 4641, Otolaryngology Unit, , University of Siena, ; Siena, Italy
[481
]Local Health Unit, Pharmaceutical Department of Grosseto, Toscana Sud Est Local Health
Unit, Grosseto, Italy
[482
]GRID grid.419504.d, ISNI 0000 0004 1760 0109, U.O.C. Laboratorio di Genetica Umana, , IRCCS Istituto Giannina Gaslini, ; Genoa, Italy
[483
]GRID grid.7548.e, ISNI 0000000121697570, Infectious Diseases Clinics, , University of Modena and Reggio Emilia, ; Modena, Italy
[485
]GRID grid.418224.9, ISNI 0000 0004 1757 9530, Department of Cardiovascular, Neural and Metabolic Sciences, , Istituto Auxologico Italiano, IRCCS, San Luca Hospital, ; Milan, Italy
[486
]GRID grid.7563.7, ISNI 0000 0001 2174 1754, Department of Medicine and Surgery, , University of Milano-Bicocca, ; Milan, Italy
[487
]GRID grid.418224.9, ISNI 0000 0004 1757 9530, Laboratory of Cardiovascular Genetics, , Istituto Auxologico Italiano, IRCCS, ; Milan, Italy
[488
]GRID grid.460094.f, ISNI 0000 0004 1757 8431, Unit of Infectious Diseases, , ASST Papa Giovanni XXIII Hospital, ; Bergamo, Italy
[489
]GRID grid.511455.1, Direzione Scientifica, , Istituti Clinici Scientifici Maugeri IRCCS, ; Pavia, Italy
[490
]GRID grid.511455.1, Department of Cardiology, , Istituti Clinici Scientifici Maugeri IRCCS, Institute of Montescano, ; Pavia, Italy
[491
]GRID grid.511455.1, Department of Cardiac Rehabilitation, , Institute of Tradate (VA) and Istituti Clinici Scientifici Maugeri IRCCS, ; Pavia, Italy
[492
]Department of Cardiology, Istituti Clinici Scientifici Maugeri IRCCS, Institute of
Milan, Milan, Italy
[493
]GRID grid.4643.5, ISNI 0000 0004 1937 0327, Department of Electronics, Information and Bioengineering (DEIB), , Politecnico di Milano, ; Milan, Italy
[495
]CNR-Consiglio Nazionale delle Ricerche, Istituto di Biologia e Biotecnologia Agraria
(IBBA), Milano, Italy
[496
]GRID grid.417623.5, ISNI 0000 0004 1758 0566, Core Research Laboratory, , ISPRO, ; Florence, Italy
[500
]GRID grid.411477.0, ISNI 0000 0004 1759 0844, Medical Genetics Unit, , Meyer Children’s University Hospital, ; Florence, Italy
[502
]GRID grid.415928.3, Pneumology Unit, Department of Medicine, , Misericordia Hospital, ; Grosseto, Italy
[503
]GRID grid.144767.7, ISNI 0000 0004 4682 2907, Intensive Care Unit and Department of Anesthesia, ASST Fatebenefratelli Sacco, , Luigi Sacco Hospital, Polo Universitario, University of Milan, ; Milan, Italy
[505
]GRID grid.158820.6, ISNI 0000 0004 1757 2611, Department of Clinical Medicine, Public Health, Life and Environment Sciences, , University of L’Aquila, ; L’Aquila, Italy
[507
]GRID grid.411477.0, ISNI 0000 0004 1759 0844, Department of Medical Sciences, Infectious and Tropical Diseases Unit, , Azienda Ospedaliera Universitaria Senese, ; Siena, Italy
[508
]GRID grid.415194.c, ISNI 0000 0004 1759 6488, Unit of Infectious Diseases, , Santa Maria Annunziata Hospital, ; Florence, Italy
[510
]GRID grid.5395.a, ISNI 0000 0004 1757 3729, Infectious Diseases Unit, Department of Clinical and Experimental Medicine, , University of Pisa, ; Pisa, Italy
[512
]GRID grid.8142.f, ISNI 0000 0001 0941 3192, Clinic of Infectious Diseases, , Catholic University of the Sacred Heart, ; Rome, Italy
[513
]GRID grid.8142.f, ISNI 0000 0001 0941 3192, Department of Diagnostic and Laboratory Medicine, Institute of Biochemistry and Clinical
Biochemistry, Fondazione Policlinico Universitario A. Gemelli IRCCS, , Catholic University of the Sacred Heart, ; Rome, Italy
[514
]GRID grid.280776.c, ISNI 0000 0004 0394 1447, Department of Population Health Sciences, , Geisinger Health System, ; Danville, PA USA
[515
]GRID grid.280776.c, ISNI 0000 0004 0394 1447, Department of Molecular and Functional Genomics, , Geisinger Health System, ; Danville, PA USA
[517
]GRID grid.280776.c, ISNI 0000 0004 0394 1447, Phenomic Analytics and Clinical Data Core, , Geisinger Health System, ; Danville, PA USA
[519
]GRID grid.418449.4, ISNI 0000 0004 0379 5398, Bradford Institute for Health Research, , Bradford Teaching Hospitals National Health Service (NHS) Foundation Trust, ; Bradford, UK
[520
]GRID grid.10306.34, ISNI 0000 0004 0606 5382, Medical and Population Genomics, , Wellcome Sanger Institute, ; Hinxton, UK
[521
]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, School of Basic and Medical Biosciences, Faculty of Life Sciences and Medicine, , King’s College London, ; London, UK
[522
]GRID grid.10306.34, ISNI 0000 0004 0606 5382, Department of Human Genetics, , Wellcome Sanger Institute, ; Hinxton, UK
[523
]GRID grid.5335.0, ISNI 0000000121885934, National Institute for Health Research Blood and Transplant Research Unit in Donor
Health and Genomics, , University of Cambridge, ; Cambridge, UK
[524
]GRID grid.5335.0, ISNI 0000000121885934, Department of Haematology, , University of Cambridge, ; Cambridge, UK
[525
]GRID grid.5335.0, ISNI 0000000121885934, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health
and Primary Care, , University of Cambridge, ; Cambridge, UK
[526
]GRID grid.5335.0, ISNI 0000000121885934, British Heart Foundation Centre of Research Excellence, , University of Cambridge, ; Cambridge, UK
[527
]GRID grid.5335.0, ISNI 0000000121885934, Health Data Research UK Cambridge, Wellcome Genome Campus, , University of Cambridge, ; Cambridge, UK
[528
]GRID grid.4830.f, ISNI 0000 0004 0407 1981, Department of Genetics, , University Medical Centre Groningen, University of Groningen, ; Groningen, The Netherlands
[529
]GRID grid.7692.a, ISNI 0000000090126352, Department of Genetics, , University Medical Centre Utrecht, ; Utrecht, The Netherlands
[530
]GRID grid.4494.d, ISNI 0000 0000 9558 4598, Department of Epidemiology, , University Medical Center Groningen, University of Groningen, ; Groningen, The Netherlands
[531
]GRID grid.4830.f, ISNI 0000 0004 0407 1981, Department of Genetics, , University Medical Centre Groningen, University of Groningen, ; Groningen, The Netherlands
[532
]GRID grid.4494.d, ISNI 0000 0000 9558 4598, Department of Psychiatry, , University Medical Center Groningen, ; Groningen, The Netherlands
[533
]GRID grid.189504.1, ISNI 0000 0004 1936 7558, Department of Biostatistics, , Boston University School of Public Health, ; Boston, MA USA
[534
]GRID grid.410370.1, ISNI 0000 0004 4657 1992, Center for Population Genomics, , MAVERIC, VA Boston Healthcare System, ; Boston, MA USA
[535
]GRID grid.410370.1, ISNI 0000 0004 4657 1992, MAVERIC, , VA Boston Healthcare System, ; Boston, MA USA
[536
]GRID grid.189967.8, ISNI 0000 0001 0941 6502, Department of Epidemiology, , Emory University Rollins School of Public Health, ; Atlanta, GA USA
[538
]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Vrije Universiteit Amsterdam, ; Amsterdam, The Netherlands
[539
]GRID grid.66859.34, ISNI 0000 0004 0546 1623, Broad Institute of MIT and Harvard, ; Boston, MA USA
[540
]GRID grid.25879.31, ISNI 0000 0004 1936 8972, Department of Genetics, , University of Pennsylvania Perelman School of Medicine, ; Philadelphia, PA USA
[541
]GRID grid.4714.6, ISNI 0000 0004 1937 0626, Department of Neuroscience, , Karolinska Institutet, ; Stockholm, Sweden
[542
]GRID grid.419518.0, ISNI 0000 0001 2159 1813, Max Planck Institute for Evolutionary Anthropology, ; Leipzig, Germany
[543
]GRID grid.8993.b, ISNI 0000 0004 1936 9457, Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, , Uppsala University, ; Uppsala, Sweden
[544
]GRID grid.8993.b, ISNI 0000 0004 1936 9457, Integrative Physiology, Department of Medical Cell Biology, , Uppsala University, ; Uppsala, Sweden
[545
]Stanley Center for Psychiatric Research and Program in Medical and Population Genetics,
Muscatine, IA USA
[546
]GRID grid.4714.6, ISNI 0000 0004 1937 0626, Division Anesthesiology and Intensive Care, CLINTEC, , Karolinska Institutet, ; Stockholm, Sweden
[547
]GRID grid.253615.6, ISNI 0000 0004 1936 9510, Department of Clinical Research and Leadership, , George Washington University, ; Washington, DC USA
[548
]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Big Data Institute, Nuffield Department of Population Health, , University of Oxford, ; Oxford, UK
[549
]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Wellcome Centre for Human Genetics, , University of Oxford, ; Oxford, UK
[550
]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Nuffield Department of Medicine, Experimental Medicine Division, , University of Oxford, John Radcliffe Hospital, ; Oxford, UK
[551
]GRID grid.120073.7, ISNI 0000 0004 0622 5016, Public Health England, Field Service, , Addenbrooke’s Hospital, ; Cambridge, UK
Author information
Athanasios Kousathanas
http://orcid.org/0000-0001-6265-6521
Erola Pairo-Castineira
http://orcid.org/0000-0002-2423-3090
Konrad Rawlik
http://orcid.org/0000-0002-0010-370X
Susan Walker
http://orcid.org/0000-0002-5016-6426
Tomas Malinauskas
http://orcid.org/0000-0002-4847-5529
Xia Shen
http://orcid.org/0000-0003-4390-1979
Katherine S. Elliott
http://orcid.org/0000-0002-8125-797X
Sean Keating
http://orcid.org/0000-0001-8552-5604
Lucija Klaric
http://orcid.org/0000-0003-3105-8929
Nick Parkinson
http://orcid.org/0000-0001-6336-5654
Alistair Nichol
http://orcid.org/0000-0002-4689-1238
Malcolm G. Semple
http://orcid.org/0000-0001-9700-0418
Shahla Salehi
http://orcid.org/0000-0002-5058-7706
Julian Knight
http://orcid.org/0000-0002-0377-5536
Greg Elgar
http://orcid.org/0000-0001-7323-1596
Christine Patch
http://orcid.org/0000-0002-4191-0663
Aris Baras
http://orcid.org/0000-0002-6830-3396
Goncalo R. Abecasis
http://orcid.org/0000-0003-1509-1825
Manuel A. R. Ferreira
http://orcid.org/0000-0001-9059-1825
Daniel J. Rader
http://orcid.org/0000-0002-9245-9876
Marylyn D. Ritchie
http://orcid.org/0000-0002-1208-1720
Manu Shankar-Hari
http://orcid.org/0000-0002-5338-2538
Charlotte Summers
http://orcid.org/0000-0002-7269-2873
Charles Hinds
http://orcid.org/0000-0001-5094-8324
Danny McAuley
http://orcid.org/0000-0002-3283-1947
Hugh Montgomery
http://orcid.org/0000-0001-8797-5019
Paul Elliott
http://orcid.org/0000-0002-7511-5684
Albert Tenesa
http://orcid.org/0000-0003-4884-4475
Lee Murphy
http://orcid.org/0000-0001-6467-7449
Kathy Rowan
http://orcid.org/0000-0001-8217-5602
Chris P. Ponting
http://orcid.org/0000-0003-0202-7816
Veronique Vitart
http://orcid.org/0000-0002-4991-3797
James F. Wilson
http://orcid.org/0000-0001-5751-9178
Jian Yang
http://orcid.org/0000-0003-2001-2474
Andrew D. Bretherick
http://orcid.org/0000-0001-9258-3140
Sara Clohisey Hendry
http://orcid.org/0000-0001-7489-9846
Loukas Moutsianas
http://orcid.org/0000-0001-5453-345X
Andy Law
http://orcid.org/0000-0003-1868-2364
Mark J. Caulfield
http://orcid.org/0000-0001-9295-3594
J. Kenneth Baillie
http://orcid.org/0000-0001-5258-793X
Article
Publisher ID: 4576DOI: 10.1038/s41586-022-04576-6
PMC ID: 9259496
PubMed ID: 35255492
SO-VID: 20684e3b-e601-4aee-9a32-37d980e127be
Copyright © © The Author(s) 2022
License:
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
History
Date
received
: 2
September
2021
Date
accepted
: 23
February
2022
Categories
Subject:
Article
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issue-copyright-statement © The Author(s), under exclusive licence to Springer Nature Limited 2022
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