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Whole-genome sequencing reveals host factors underlying critical COVID-19

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dc.contributor.authorKousathanas, Athanasios
dc.contributor.authorPairo-Castineira, Erola
dc.contributor.authorRawlik, Konrad
dc.contributor.authorStuckey, Alex
dc.contributor.authorOdhams, Christopher A.
dc.contributor.authorWalker, Susan
dc.contributor.authorRussell, Clark D.
dc.contributor.authorMalinauskas, Tomas
dc.contributor.authorWu, Yang
dc.contributor.authorMillar, Jonathan
dc.contributor.authorShen, Xia
dc.contributor.authorElliott, Katherine S.
dc.contributor.authorGriffiths, Fiona
dc.contributor.authorOosthuyzen, Wilna
dc.contributor.authorMorrice, Kirstie
dc.contributor.authorKeating, Sean
dc.contributor.authorWang, Bo
dc.contributor.authorRhodes, Daniel
dc.contributor.authorKlaric, Lucija
dc.contributor.authorZechner, Marie
dc.contributor.authorParkinson, Nick
dc.contributor.authorSiddiq, Afshan
dc.contributor.authorGoddard, Peter
dc.contributor.authorDonovan, Sally
dc.contributor.authorMaslove, David
dc.contributor.authorNichol, Alistair
dc.contributor.authorSemple, Malcolm G.
dc.contributor.authorZainy, Tala
dc.contributor.authorMaleady-Crowe, Fiona
dc.contributor.authorTodd, Linda
dc.contributor.authorSalehi, Shahla
dc.contributor.authorKnight, Julian
dc.contributor.authorElgar, Greg
dc.contributor.authorChan, Georgia
dc.contributor.authorArumugam, Prabhu
dc.contributor.authorPatch, Christine
dc.contributor.authorRendon, Augusto
dc.contributor.authorBentley, David
dc.contributor.authorKingsley, Clare
dc.contributor.authorKosmicki, Jack A.
dc.contributor.authorHorowitz, Julie E.
dc.contributor.authorBaras, Aris
dc.contributor.authorAbecasis, Goncalo R.
dc.contributor.authorFerreira, Manuel A.R.
dc.contributor.authorJustice, Anne
dc.contributor.authorMirshahi, Tooraj
dc.contributor.authorOetjens, Matthew
dc.contributor.authorRader, Daniel J.
dc.contributor.authorRitchie, Marylyn D.
dc.contributor.authorVerma, Anurag
dc.contributor.authorGenOMICC investigators
dc.contributor.author23andMe investigators
dc.contributor.authorCOVID-Human Genetics Initiative
dc.contributor.authorKaye, Callum
dc.contributor.authorCaulfield, Mark
dc.contributor.authorBaillie, J Kenneth
dc.contributor.institutionUniversity of Aberdeen.Aberdeen Centre for Evaluationen
dc.date.accessioned2023-09-25T14:58:01Z
dc.date.available2023-09-25T14:58:01Z
dc.date.issued2022-07-07
dc.descriptionFunding Information: We thank the patients and their loved ones who volunteered to contribute to this study at one of the most difficult times in their lives, and the research staff in every intensive care unit who recruited patients at personal risk under challenging conditions. GenOMICC was funded by the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council (MRC), UKRI, Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (J.K.B., 223164/Z/21/Z) a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. WGS was performed by Illumina at Illumina Laboratory Services and was overseen by Genomics England. We would like to thank all at Genomics England who have contributed to the sequencing, clinical and genomic data analysis. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref. MC_PC_20029). A.D.B. would like to acknowledge funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z) and the Edinburgh Clinical Academic Track (ECAT) programme. We thank the research participants and employees of 23andMe for making this work possible. Genomics England and the 100,000 Genomes Project were funded by the National Institute for Health Research, the Wellcome Trust, the MRC, Cancer Research UK, the DHSC and NHS England. We are grateful for the support from S. Hill and the team in NHS England and the 13 Genomic Medicine Centres that delivered the 100,000 Genomes Project, which provided most of the control genome sequences for this study. We thank the participants in the 100,000 Genomes Project, who made this study possible, and the Genomics England Participant Panel for their strategic advice, involvement and engagement. We acknowledge NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre, who provided life-course longitudinal clinical data on the participants. This work forms part of the portfolio of research of the National Institute for Health Research Barts Biomedical Research Centre. Mark Caulfield is an NIHR Senior Investigator. This study owes a great deal to the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. Additional replication was conducted using the UK Biobank Resource (project 26041). The Penn Medicine BioBank is funded by a gift from the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health under CTSA award number UL1TR001878; and the Perelman School of Medicine at the University of Pennsylvania. We thank the AncestryDNA customers who voluntarily contributed information in the COVID-19 survey. HRS (dbGaP accession: phs000428.v1.p1): HRS was supported by the National Institute on Aging (NIA U01AG009740). The genotyping was funded separately by the National Institute on Aging (RC2 AG036495, RC4 AG039029). Genotyping was conducted by the NIH Center for Inherited Disease Research (CIDR) at Johns Hopkins University. Genotyping quality control and final preparation of the data were performed by the Genetics Coordinating Center at the University of Washington. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by the NCI, NHGRI, NHLBI, NIDA, NIMH and NINDS. The data used for the analyses described in this manuscript were obtained from the GTEx Portal on 22 August 2021 (GTEx Analysis Release v.8 (dbGaP Accession phs000424.v8.p2). We thank the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available at https://www.covid19hg.org/acknowledgements . The views expressed are those of the authors and not necessarily those of the DHSC, NHS, Department for International Development (DID), NIHR, MRC, Wellcome Trust or Public Health England.en
dc.description.statusPeer revieweden
dc.format.extent7
dc.format.extent8193682
dc.identifier281315613
dc.identifier5e5e77da-dc53-430e-a7a7-06920224867b
dc.identifier85134361378
dc.identifier35255492
dc.identifier.citationKousathanas, A, Pairo-Castineira, E, Rawlik, K, Stuckey, A, Odhams, C A, Walker, S, Russell, C D, Malinauskas, T, Wu, Y, Millar, J, Shen, X, Elliott, K S, Griffiths, F, Oosthuyzen, W, Morrice, K, Keating, S, Wang, B, Rhodes, D, Klaric, L, Zechner, M, Parkinson, N, Siddiq, A, Goddard, P, Donovan, S, Maslove, D, Nichol, A, Semple, M G, Zainy, T, Maleady-Crowe, F, Todd, L, Salehi, S, Knight, J, Elgar, G, Chan, G, Arumugam, P, Patch, C, Rendon, A, Bentley, D, Kingsley, C, Kosmicki, J A, Horowitz, J E, Baras, A, Abecasis, G R, Ferreira, M A R, Justice, A, Mirshahi, T, Oetjens, M, Rader, D J, Ritchie, M D, Verma, A, GenOMICC investigators, 23andMe investigators, COVID-Human Genetics Initiative, Kaye, C, Caulfield, M & Baillie, J K 2022, 'Whole-genome sequencing reveals host factors underlying critical COVID-19', Nature, vol. 607, no. 7917, pp. 97-103. https://doi.org/10.1038/s41586-022-04576-6en
dc.identifier.doi10.1038/s41586-022-04576-6
dc.identifier.iss7917en
dc.identifier.issn0028-0836
dc.identifier.otherORCID: /0000-0002-6904-7048/work/174358360
dc.identifier.urihttps://hdl.handle.net/2164/21742
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85134361378&partnerID=8YFLogxKen
dc.identifier.vol607en
dc.language.isoeng
dc.relation.ispartofNatureen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.subjectGenetics researchen
dc.subjectGenome-wide association studiesen
dc.subjectInfectious diseasesen
dc.subjectRespiratory distress syndromeen
dc.subjectSARS-CoV-2en
dc.subjectR Medicineen
dc.subjectQH426 Geneticsen
dc.subjectGeneralen
dc.subjectMedical Research Council (MRC)en
dc.subjectUK Research and Innovation (UKRI)en
dc.subjectPC_20004, MC_PC_19025en
dc.subjectMC_PC_1905en
dc.subjectMRNO2995X/en
dc.subjectMC_PC_20029en
dc.subjectWellcome Trusten
dc.subject223164/Z/21/Zen
dc.subject204979/Z/16/Zen
dc.subjectBiotechnology and Biological Sciences Research Council (BBSRC)en
dc.subjectBBS/E/D/20002172en
dc.subjectBBS/E/D/10002070en
dc.subjectBBS/E/D/30002275en
dc.subjectNational Institute for Health Research (NIHR)en
dc.subjectSupplementary Dataen
dc.subject.lccRen
dc.subject.lccQH426en
dc.titleWhole-genome sequencing reveals host factors underlying critical COVID-19en
dc.typeJournal articleen

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