Evidence map›Paper›PMID 25533491›Full record

Observational studyThe Lancet. Respiratory medicine2015

Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study.

Anna Rautanen, Tara C Mills, Anthony C Gordon, Paula Hutton, Michael Steffens, Rosamond Nuamah, Jean-Daniel Chiche, Tom Parks, Stephen J Chapman, Emma E Davenport and 29 more

Registry-linked trialOpen access · hybridAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in The Lancet. Respiratory medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05336851 (Emergency PanorOmic Wide Association Study in Respiratory Infectious Disease), which is not on this map. Cited by 110 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed, 6 pooled it
9.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05336851 recruitingnot on this mapstarted 2023, after this paper: background citation

Emergency PanorOmic Wide Association Study in Respiratory Infectious Disease (ePWAS-RID)

Typeobservational_patient_registrySponsorThe University of Hong KongRan2023 to 2028Enrolled2,000ConditionsViral Infections, Bacterial Infections, Fungal Infections, Mixed InfectionArmsBiomarker blood draw and saliva collection
3 · Its place in the literature

Who cites it

110 citing papers in PubMed, 6 syntheses or guidelines pooled it, 198 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Association between the Lymphotoxin-BioMed research international · 2020
    Pooled it
  5. LBP rs2232618 polymorphism contributes to risk of sepsis after trauma.World journal of emergency surgery : WJES · 2018
    Pooled it
  6. Pooled it
  7. Trial
  8. Susceptibility to Childhood Pneumonia: A Genome-Wide Analysis.American journal of respiratory cell and molecular biology · 2017
    Trial
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Genetic associations in sepsis and ARDS.Frontiers in pharmacology · 2026
    Review
  17. Immunosenescence and susceptibility to respiratory viruses: a state-of-the-art review.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  18. Review
  19. Review
  20. Article

50 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

39 authors at 20 institutions in 11 countries.

Anna RautanenWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. Electronic address: anna.rautanen@well.ox.ac.uk.
Tara C MillsWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Anthony C GordonImperial College London, London, UK.
Paula HuttonJohn Radcliffe Hospital, Oxford, UK.
Michael SteffensInstitute for Medical Biometry, Informatics and Epidemiology (IMBIE) of the University of Bonn, Bonn, Germany.
Rosamond NuamahWilliam Harvey Research Institute, Barts and The London School of Medicine Queen Mary University of London, London, UK.
Jean-Daniel ChicheHospital Cochin, Paris, France.
Tom ParksWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Stephen J ChapmanWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Emma E DavenportWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Katherine S ElliottWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Julian BionSchool of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK.
Peter LichtnerInstitute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Thomas MeitingerInstitute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Technische Universität München, Institute of Human Genetics, Munich, Germany.
Thomas F WienkerInstitute for Medical Biometry, Informatics and Epidemiology (IMBIE) of the University of Bonn, Bonn, Germany.
Mark J CaulfieldWilliam Harvey Research Institute, Barts and The London School of Medicine Queen Mary University of London, London, UK.
Charles MeinWilliam Harvey Research Institute, Barts and The London School of Medicine Queen Mary University of London, London, UK.
Frank BloosJena University Hospital and Center for Sepsis Control and Care, Jena, Germany.
Ilona BobekNational Health Service Centre, Budapest, Hungary.
Paolo CotogniUniversity of Torino, Turin, Italy.
Vladimir SramekMedical Faculty of Mazaryk University, Brno, Czech Republic.
Silver SarapuuTartu University Hospital, Tartu, Estonia.
Makbule KobilayUniversity of Bonn, Bonn, Germany.
V Marco RanieriUniversity of Torino, Turin, Italy.
Jordi RelloCIBERES, Vall d'Hebron Institute of Research, Universitat Autonoma de Barcelona, Barcelona, Spain.
Gonzalo SirgoJoan XXIII University Hospital, Pere Virgili Health Institute, University Rovirai Virgili, Tarragona, Spain.
Yoram G WeissHadassah Medical Centre, Jerusalem, Israel.
Stefan RusswurmJena University Hospital, Jena, Germany.
E Marion SchneiderSection of Experimental Anesthesiology, University Hospital, Ulm, Germany.
Konrad ReinhartJena University Hospital and Center for Sepsis Control and Care, Jena, Germany.
Paul A H HollowayImperial College London, London, UK.
Julian C KnightWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Chris S GarrardJohn Radcliffe Hospital, Oxford, UK.
James A RussellUniversity of British Columbia, Vancouver, BC, Canada.
Keith R WalleyUniversity of British Columbia, Vancouver, BC, Canada.
Frank StüberDepartment of Anaesthesiology and Pain Medicine, Bern University Hospital, and University of Bern, Switzerland.
Adrian V S HillWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Charles J HindsWilliam Harvey Research Institute, Barts and The London School of Medicine Queen Mary University of London, London, UK.
ESICM/ECCRN GenOSept Investigators
Centre for Human Genetics · GBJena University Hospital · DEQueen Mary University of London · GBImperial College London · GBInstitut für Medizinische Biometrie, Informatik und Epidemiologie · DEJohn Radcliffe Hospital · GBUniversity of British Columbia · CAUniversity of Oxford · GBUniversity of Turin · ITCentro de Investigación Biomédica en Red · ESHadassah Medical Center · ILHelmholtz Zentrum München · DEHôpital Cochin · FRInstitut d'Investigació Sanitària Pere Virgili · ESMasaryk University · CZNational Public Health and Medical Officer Service · HUTartu University Hospital · EETechnical University of Munich · DEUniversity Hospital Ulm · DEUniversity of Bern · CH

Funding

Department of Health NIHR/CS/009/007European Research Council 294557Medical Research Council G0900747Medical Research Council G1001712Medical Research Council G1100449Medical Research Council G9521010Medical Research Council MR/K006584/1Wellcome TrustWellcome Trust 090532/Z/09/Z
6 · The paper itself

Abstract

backgroundSepsis continues to be a major cause of death, disability, and health-care expenditure worldwide. Despite evidence suggesting that host genetics can influence sepsis outcomes, no specific loci have yet been convincingly replicated. The aim of this study was to identify genetic variants that influence sepsis survival.

methodsWe did a genome-wide association study in three independent cohorts of white adult patients admitted to intensive care units with sepsis, severe sepsis, or septic shock (as defined by the International Consensus Criteria) due to pneumonia or intra-abdominal infection (cohorts 1-3, n=2534 patients). The primary outcome was 28 day survival. Results for the cohort of patients with sepsis due to pneumonia were combined in a meta-analysis of 1553 patients from all three cohorts, of whom 359 died within 28 days of admission to the intensive-care unit. The most significantly associated single nucleotide polymorphisms (SNPs) were genotyped in a further 538 white patients with sepsis due to pneumonia (cohort 4), of whom 106 died.

findingsIn the genome-wide meta-analysis of three independent pneumonia cohorts (cohorts 1-3), common variants in the FER gene were strongly associated with survival (p=9·7 × 10(-8)). Further genotyping of the top associated SNP (rs4957796) in the additional cohort (cohort 4) resulted in a combined p value of 5·6 × 10(-8) (odds ratio 0·56, 95% CI 0·45-0·69). In a time-to-event analysis, each allele reduced the mortality over 28 days by 44% (hazard ratio for death 0·56, 95% CI 0·45-0·69; likelihood ratio test p=3·4 × 10(-9), after adjustment for age and stratification by cohort). Mortality was 9·5% in patients carrying the CC genotype, 15·2% in those carrying the TC genotype, and 25·3% in those carrying the TT genotype. No significant genetic associations were identified when patients with sepsis due to pneumonia and intra-abdominal infection were combined.

interpretationWe have identified common variants in the FER gene that associate with a reduced risk of death from sepsis due to pneumonia. The FER gene and associated molecular pathways are potential novel targets for therapy or prevention and candidates for the development of biomarkers for risk stratification.

fundingEuropean Commission and the Wellcome Trust.

Indexed as

Cohort StudiesFemaleGenetic MarkersGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedPneumoniaProtein-Tyrosine KinasesSepsisSurvival AnalysisGenetic MarkersProtein-Tyrosine Kinasesproto-oncogene protein c-fes-fps

Identifiers

PMID25533491
PMCPMC4314768
OpenAlexW2167320417

What Socratic holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.