Evidence map›Paper›PMID 31276585›Full record

ArticleHuman molecular genetics2019

Integrating Mendelian randomization and multiple-trait colocalization to uncover cell-specific inflammatory drivers of autoimmune and atopic disease.

Lucy M McGowan, George Davey Smith, Tom R Gaunt, Tom G Richardson

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

30 citing papers in PubMed, 38 citations in OpenAlex.

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  19. Interleukin-18 and COVID-19.Epidemiology and infection · 2021
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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

4 authors at 1 institution in 1 country.

Lucy M McGowanSchool of Physiology, Pharmacology and Neuroscience, Faculty of Life Sciences, University of Bristol, Bristol, BS8 1TD, UK.
George Davey SmithMRC Integrative Epidemiology Unit, Population Health Sciences Institute, University of Bristol, Bristol, BS8 2BN, UK.
Tom R GauntMRC Integrative Epidemiology Unit, Population Health Sciences Institute, University of Bristol, Bristol, BS8 2BN, UK.
Tom G RichardsonMRC Integrative Epidemiology Unit, Population Health Sciences Institute, University of Bristol, Bristol, BS8 2BN, UK.
University of Bristol · GB

Funding

Medical Research Council MC_UU_00011/1Medical Research Council MC_UU_00011/4Medical Research Council MR/S003886/1Wellcome Trust
6 · The paper itself

Abstract

Immune-mediated diseases (IMDs) arise when tolerance is lost and chronic inflammation is targeted towards healthy tissues. Despite their growing prevalence, therapies to treat IMDs are lacking. Cytokines and their receptors orchestrate inflammatory responses by regulating elaborate signalling networks across multiple cell types making it challenging to pinpoint therapeutically relevant drivers of IMDs. We developed an analytical framework that integrates Mendelian randomization (MR) and multiple-trait colocalization (moloc) analyses to highlight putative cell-specific drivers of IMDs. MR evaluated causal associations between the levels of 10 circulating cytokines and 9 IMDs within human populations. Subsequently, we undertook moloc analyses to assess whether IMD trait, cytokine protein and corresponding gene expression are driven by a shared causal variant. Moreover, we leveraged gene expression data from three separate cell types (monocytes, neutrophils and T cells) to discern whether associations may be attributed to cell type-specific drivers of disease. MR analyses supported a causal role for IL-18 in inflammatory bowel disease (IBD) (P = 1.17 × 10-4) and eczema/dermatitis (P = 2.81 × 10-3), as well as associations between IL-2rα and IL-6R with several other IMDs. Moloc strengthened evidence of a causal association for these results, as well as providing evidence of a monocyte and neutrophil-driven role for IL-18 in IBD pathogenesis. In contrast, IL-2rα and IL-6R associations were found to be T cell specific. Our analytical pipeline can help to elucidate putative molecular pathways in the pathogeneses of IMDs, which could be applied to other disease contexts.

Indexed as

CytokinesEczemaGene Expression RegulationHumansInflammatory Bowel DiseasesInterleukin-18Interleukin-2 Receptor alpha SubunitMendelian Randomization AnalysisQuantitative Trait LociReceptors, Interleukin-6T-LymphocytesCytokinesIL18 protein, humanIL2RA protein, humanIL6R protein, humanInterleukin-18Interleukin-2 Receptor alpha SubunitReceptors, Interleukin-6

Identifiers

PMID31276585
PMCPMC6859431
OpenAlexW2955756538

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.