Evidence map›Paper›PMID 36018815›Full record

ArticleHuman molecular genetics2023

Large registry-based analysis of genetic predisposition to tuberculosis identifies genetic risk factors at HLA.

Anniina Tervi, Nella Junna, Martin Broberg, Samuel E Jones, FinnGen, Satu Strausz, Hanna-Riikka Kreivi, Caroline A Heckman, Hanna M Ollila

Open access · hybridAbstract read
In one paragraph

Article in Human molecular genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
0.3field-weighted citation impact, top 45% 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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  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

9 authors at 2 institutions in 2 countries.

Anniina TerviInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-9857-2132
Nella JunnaInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-5953-5523
Martin BrobergInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-5419-9479
Samuel E JonesInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.ORCID 0000-0003-0153-922X
FinnGen
Satu StrauszInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.ORCID 0000-0001-6778-4848
Hanna-Riikka KreiviDepartment of Pulmonology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.ORCID 0000-0002-9361-8322
Caroline A HeckmanInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-4324-8706
Hanna M OllilaInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-5302-6429
University of Helsinki · FIBroad Institute · US

Funding

Medical Research Council MC_PC_17228Medical Research Council MC_QA137853
6 · The paper itself

Abstract

Tuberculosis is a significant public health concern resulting in the death of over 1 million individuals each year worldwide. While treatment options and vaccines exist, a substantial number of infections still remain untreated or are caused by treatment resistant strains. Therefore, it is important to identify mechanisms that contribute to risk and prognosis of tuberculosis as this may provide tools to understand disease mechanisms and provide novel treatment options for those with severe infection. Our goal was to identify genetic risk factors that contribute to the risk of tuberculosis and to understand biological mechanisms and causality behind the risk of tuberculosis. A total of 1895 individuals in the FinnGen study had International Classification of Diseases-based tuberculosis diagnosis. Genome-wide association study analysis identified genetic variants with statistically significant association with tuberculosis at the human leukocyte antigen (HLA) region (P < 5e-8). Fine mapping of the HLA association provided evidence for one protective haplotype tagged by HLA DQB1*05:01 (P = 1.82E-06, OR = 0.81 [CI 95% 0.74-0.88]), and predisposing alleles tagged by HLA DRB1*13:02 (P = 0.00011, OR = 1.35 [CI 95% 1.16-1.57]). Furthermore, genetic correlation analysis showed association with earlier reported risk factors including smoking (P < 0.05). Mendelian randomization supported smoking as a risk factor for tuberculosis (inverse-variance weighted P < 0.05, OR = 1.83 [CI 95% 1.15-2.93]) with no significant evidence of pleiotropy. Our findings indicate that specific HLA alleles associate with the risk of tuberculosis. In addition, lifestyle risk factors such as smoking contribute to the risk of developing tuberculosis.

Indexed as

Genetic Predisposition to DiseaseTuberculosisAllelesGene FrequencyGenome-Wide Association StudyHaplotypesHLA-DQ beta-ChainsHLA-DRB1 ChainsHumansRisk FactorsHLA-DQ beta-ChainsHLA-DRB1 Chains

Identifiers

PMID36018815
PMCPMC9838093
OpenAlexW4293149736

What OpenQuestion holds

Textmetadata
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.