Evidence map›Paper›PMID 31462703›Full record

ArticleGenes and immunity2020

Elevated risk of invasive group A streptococcal disease and host genetic variation in the human leucocyte antigen locus.

Tom Parks, Katherine Elliott, Theresa Lamagni, Kathryn Auckland, Alexander J Mentzer, Rebecca Guy, Doreen Cartledge, Lenka Strakova, Daniel O' Connor, Andrew J Pollard and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genes and immunity, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Trial
  2. Review
  3. Review
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Tom ParksWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-1163-8654
Katherine ElliottWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Theresa LamagniNational Infection Service, Public Health England, London, UK.
Kathryn AucklandWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Alexander J MentzerWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-4502-2209
Rebecca GuyNational Infection Service, Public Health England, London, UK.ORCID http://orcid.org/0000-0001-5500-5691
Doreen CartledgeLee Spark Necrotising Fasciitis Foundation, Lytham St Annes, UK.
Lenka StrakovaDepartment of Microbiology, Portsmouth Hospitals NHS Trust, Portsmouth, UK.
Daniel O' ConnorOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-6902-9886
Andrew J PollardOxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Matthew J NevilleNational Institute for Health Research Oxford Biomedical Research Centre, Oxford, UK.ORCID http://orcid.org/0000-0002-6004-5433
Anubha MahajanWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Houman AshrafianDivision of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Stephen J ChapmanAdult Cystic Fibrosis Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Adrian V S HillWellcome Centre for Human Genetics, University of Oxford, Oxford, UK. adrian.hill@ndm.ox.ac.uk.ORCID http://orcid.org/0000-0003-0900-9629
Shiranee SriskandanNational Institute for Health Research Health Protection Research Unit in Healthcare-Associated Infection & Antimicrobial Resistance, Imperial College London, London, UK. s.sriskandan@imperial.ac.uk.
Julian C KnightWellcome Centre for Human Genetics, University of Oxford, Oxford, UK. julian.knight@well.ox.ac.uk.ORCID http://orcid.org/0000-0002-0377-5536

Funding

Department of Health ACF-2016-20-001Medical Research Council G1100449Wellcome TrustWellcome Trust 090532/Z/09/ZWellcome Trust 203141/Z/16/ZWellcome Trust 204969/Z/16/Z
6 · The paper itself

Abstract

Invasive group A streptococcal (GAS) disease is uncommon but carries a high case-fatality rate relative to other infectious diseases. Given the ubiquity of mild GAS infections, it remains unclear why healthy individuals will occasionally develop life-threatening infections, raising the possibility of host genetic predisposition. Here, we present the results of a case-control study including 43 invasive GAS cases and 1540 controls. Using HLA imputation and linear mixed models, we find each copy of the HLA-DQA1*01:03 allele associates with a twofold increased risk of disease (odds ratio 2.3, 95% confidence interval 1.3-4.4, P = 0.009), an association which persists with classical HLA typing of a subset of cases and analysis with an alternative large control dataset with validated HLA data. Moreover, we propose the association is driven by the allele itself rather than the background haplotype. Overall this finding provides impetus for further investigation of the immunogenetic basis of this devastating bacterial disease.

Indexed as

AdultCase-Control StudiesFemaleGene FrequencyGenes, MHC Class IIGenetic Predisposition to DiseaseHaplotypesHistocompatibility Antigens Class IHLA AntigensHLA-DQ alpha-ChainsHumansMaleMiddle AgedOdds RatioPolymorphism, Single NucleotideRisk FactorsHistocompatibility Antigens Class IHLA AntigensHLA-DQA1 antigenHLA-DQ alpha-Chains

Identifiers

PMID31462703
PMCPMC7039814

What OpenQuestion holds

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Registered trials

None linked

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 OpenQuestion graph.