Evidence map›Paper›PMID 34059071›Full record

ArticleJournal of translational medicine2021

A large-scale investigation into the role of classical HLA loci in multiple types of severe infections, with a focus on overlaps with autoimmune and mental disorders.

Ron Nudel, Rosa Lundbye Allesøe, Wesley K Thompson, Thomas Werge, Simon Rasmussen, Michael E Benros

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.0field-weighted citation impact, top 22% 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.

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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Identification of key genes and development of an identifying machine learning model for sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Article
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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

6 authors at 2 institutions in 2 countries.

Ron NudelInstitute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.ORCID 0000-0003-2309-011X
Rosa Lundbye AllesøeiPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
Wesley K ThompsonInstitute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
Thomas WergeInstitute of Biological Psychiatry, Mental Health Centre Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark.
Simon RasmussenNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Michael E BenrosiPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark. Michael.Eriksen.Benros@regionh.dk.ORCID 0000-0003-4939-9465
University of Copenhagen · DKMental Health Services · DK

Funding

2/4-Psychiatric GWAS Consortium: Genomic Follow-Up Next-Gen Sequencing & GenotypiU01MH094432 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI DALY, MARK JOSEPH · 2012 to 2015
$3.0M
NIMH NIH HHS U01 MH094432
6 · The paper itself

Abstract

backgroundInfections are a major disease burden worldwide. While they are caused by external pathogens, host genetics also plays a part in susceptibility to infections. Past studies have reported diverse associations between human leukocyte antigen (HLA) alleles and infections, but many were limited by small sample sizes and/or focused on only one infection.

methodsWe performed an immunogenetic association study examining 13 categories of severe infection (bacterial, viral, central nervous system, gastrointestinal, genital, hepatitis, otitis, pregnancy-related, respiratory, sepsis, skin infection, urological and other infections), as well as a phenotype for having any infection, and seven classical HLA loci (HLA-A, B, C, DPB1, DQA1, DQB1 and DRB1). Additionally, we examined associations between infections and specific alleles highlighted in our previous studies of psychiatric disorders and autoimmune disease, as these conditions are known to be linked to infections.

resultsAssociations between HLA loci and infections were generally not strong. Highlighted associations included associations between DQB1*0302 and DQB1*0604 and viral infections (P = 0.002835 and P = 0.014332, respectively), DQB1*0503 and sepsis (P = 0.006053), and DQA1*0301 with "other" infections (a category which includes infections not included in our main categories e.g. protozoan infections) (P = 0.000369). Some HLA alleles implicated in autoimmune diseases showed association with susceptibility to infections, but the latter associations were generally weaker, or with opposite trends (in the case of HLA-C alleles, but not with alleles of HLA class II genes). HLA alleles associated with psychiatric disorders did not show association with susceptibility to infections.

conclusionsOur results suggest that classical HLA alleles do not play a large role in the etiology of severe infections. The discordant association trends with autoimmune disease for some alleles could contribute to mechanistic theories of disease etiology.

Indexed as

HLA-A AntigensMental DisordersAllelesGene FrequencyGenetic Predisposition to DiseaseHaplotypesHLA-DQ beta-ChainsHLA-DRB1 ChainsHumansHLA-A AntigensHLA-DQ beta-ChainsHLA-DRB1 ChainsAssociation studyAutoimmune diseaseHLAImmunogeneticsInfectionsMHCPsychiatric disorder

Identifiers

PMID34059071
PMCPMC8165335
OpenAlexW3164525977

What OpenQuestion holds

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LicenceCC BY
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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.