Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
32755526
TITLE
Septic Shock: A Genomewide Association Study and Polygenic Risk Score Analysis.
ABSTRACT
Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10-10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10-6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10-3; p = 2.29 × 10-3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10-3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
DATE PUBLISHED
2020 Aug 05
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2020/08/07 06:00
pubmed 2020/08/07 06:00
medline 2020/08/07 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
D'Urso S D'Urso Shannon S The University of Queensland Diamantina Institute, University of Queensland, Brisbane, Australia.
Rajbhandari D Rajbhandari Dorrilyn D The George Institute for Global Health, Sydney, Australia.
Peach E Peach Elizabeth E The University of Queensland Diamantina Institute, University of Queensland, Brisbane, Australia.
de Guzman E de Guzman Erika E Australian Translational Genomics Centre, Queensland University of Technology, Brisbane, Australia.
Li Q Li Qiang Q The George Institute for Global Health, Sydney, Australia.
Medland SE Medland Sarah E SE QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Gordon SD Gordon Scott D SD QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Australia.
CHARGE Inflammation Working Group
Ligthart S Ligthart Symen S Department of Intensive Care, Erasmus University Medical Center, Rotterdam, The Netherlands.
Brown MA Brown Matthew A MA Guy's & St Thomas' NHS Foundation Trust and King's College London NIHR Biomedical Research Centre, London, England.
Powell J Powell Joseph J UNSW Cellular Genomics Futures Institute, University of New South Wales, Sydney, Australia.
McArthur C McArthur Colin C Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand.
Rhodes A Rhodes Andrew A Department of Adult Critical Care, St George's University Hospitals NHS Foundation Trust and St George's University of London, London, UK.
Meyer J Meyer Jason J Intensive Care Unit, Princess Alexandra Hospital, Brisbane, Australia.
Finfer S Finfer Simon S The George Institute for Global Health, Sydney, Australia.
Myburgh J Myburgh John J The George Institute for Global Health, Sydney, Australia.
Blumenthal A Blumenthal Antje A The University of Queensland Diamantina Institute, University of Queensland, Brisbane, Australia.
Cohen J Cohen Jeremy J Faculty of Medicine, University of Queensland, Brisbane, Australia.
Venkatesh B Venkatesh Balasubramanian B Faculty of Health, University of New South Wales, Sydney, Australia.
Cuellar-Partida G Cuellar-Partida Gabriel G The University of Queensland Diamantina Institute, University of Queensland, Brisbane, Australia.
Evans DM Evans David M DM Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Twin research and human genetics : the official journal of the International Society for Twin Studies
ISOABBREVIATION: Twin Res Hum Genet
YEAR: 2020
MONTH: Aug
DAY: 05
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1832-4274
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Twin Res Hum Genet
COUNTRY: England
ISSNLINKING: 1832-4274
NLMUNIQUEID: 101244624
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
Genetic association study
genetic risk scores
genomics
sepsis
septic shock
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's