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| PMID |
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| TITLE |
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| Septic Shock: A Genomewide Association Study and Polygenic Risk Score Analysis. |
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| ABSTRACT |
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| 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. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| pubmed |
2020/08/07 06:00 |
| medline |
2020/08/07 06:00 |
| entrez |
2020/08/07 06:00 |
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| AUTHORS |
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| 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 |
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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 |
|
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|
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| Ligthart S |
|
Ligthart |
Symen |
S |
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Department of Intensive Care, Erasmus University Medical Center, Rotterdam, The Netherlands. |
| Brown MA |
|
Brown |
Matthew A |
MA |
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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 |
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Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand. |
| Rhodes A |
|
Rhodes |
Andrew |
A |
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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 |
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Intensive Care Unit, Princess Alexandra Hospital, Brisbane, Australia. |
| Finfer S |
|
Finfer |
Simon |
S |
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The George Institute for Global Health, Sydney, Australia. |
| Myburgh J |
|
Myburgh |
John |
J |
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The George Institute for Global Health, Sydney, Australia. |
| Blumenthal A |
|
Blumenthal |
Antje |
A |
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The University of Queensland Diamantina Institute, University of Queensland, Brisbane, Australia. |
| Cohen J |
|
Cohen |
Jeremy |
J |
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Faculty of Medicine, University of Queensland, Brisbane, Australia. |
| Venkatesh B |
|
Venkatesh |
Balasubramanian |
B |
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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 |
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Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, UK. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: 23 |
| ISSUE: 4 |
| TITLE: Twin research and human genetics : the official journal of the International Society for Twin Studies |
| ISOABBREVIATION: Twin Res Hum Genet |
| YEAR: 2020 |
| MONTH: 08 |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1832-4274 |
| ISSNTYPE: Print |
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| MEDLINE JOURNAL |
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| MEDLINETA: Twin Res Hum Genet |
| COUNTRY: England |
| ISSNLINKING: 1832-4274 |
| NLMUNIQUEID: 101244624 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GRANTID |
AGENCY |
COUNTRY |
| MC_UU_12013/4 |
Medical Research Council |
United Kingdom |
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| GENERAL NOTE |
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| KEYWORDS |
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| KEYWORD |
| Genetic association study |
| genetic risk scores |
| genomics |
| sepsis |
| septic shock |
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| MESH HEADINGS |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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| OTHER ID's |
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