Evidence map›Paper›PMID 27814507›Full record

ArticleCell2016

A Functional Genomics Approach to Understand Variation in Cytokine Production in Humans.

Yang Li, Marije Oosting, Sanne P Smeekens, Martin Jaeger, Raul Aguirre-Gamboa, Kieu T T Le, Patrick Deelen, Isis Ricaño-Ponce, Teske Schoffelen, Anne F M Jansen and 13 more

Open access · bronzeAbstract read
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In one paragraph

Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 211 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
211citing papers in PubMed, 10 pooled it
27.6field-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.

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

211 citing papers in PubMed, 10 syntheses or guidelines pooled it, 337 citations in OpenAlex.

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  9. Integration ofFrontiers in immunology · 2023
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  10. Shared DNA methylation signatures in childhood allergy: The MeDALL study.The Journal of allergy and clinical immunology · 2021
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151 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 5 institutions in 3 countries.

Yang LiDepartment of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands. Electronic address: y.li01@umcg.nl.
Marije OostingDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 HP Nijmegen, the Netherlands.
Sanne P SmeekensDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 HP Nijmegen, the Netherlands.
Martin JaegerDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 HP Nijmegen, the Netherlands.
Raul Aguirre-GamboaDepartment of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
Kieu T T LeDepartment of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
Patrick DeelenDepartment of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands; Genomics Coordination Center, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
Isis Ricaño-PonceDepartment of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
Teske SchoffelenDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 HP Nijmegen, the Netherlands.
Anne F M JansenDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 HP Nijmegen, the Netherlands.
Morris A SwertzDepartment of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands; Genomics Coordination Center, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
Sebo WithoffDepartment of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
Esther van de VosseDepartment of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
Marcel van DeurenDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 HP Nijmegen, the Netherlands.
Frank van de VeerdonkDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 HP Nijmegen, the Netherlands.
Alexandra ZhernakovaDepartment of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
Jos W M van der MeerDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 HP Nijmegen, the Netherlands.
Ramnik J XavierCenter for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA; Broad Institute of MIT and Harvard University, Cambridge, MA 02142, USA.
Lude FrankeDepartment of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands.
Leo A B JoostenDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 HP Nijmegen, the Netherlands. Electronic address: leo.joosten@radboudumc.nl.
Cisca WijmengaDepartment of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands; Department of Immunology, University of Oslo, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway. Electronic address: c.wijmenga@umcg.nl.
Vinod KumarDepartment of Genetics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, the Netherlands. Electronic address: v.kumar@umcg.nl.
Mihai G NeteaDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 HP Nijmegen, the Netherlands. Electronic address: mihai.netea@radboudumc.nl.
Radboud University Nijmegen · NLUniversity Medical Center Groningen · NLBroad Institute · USLeiden University Medical Center · NLOslo University Hospital · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

As part of the Human Functional Genomics Project, which aims to understand the factors that determine the variability of immune responses, we investigated genetic variants affecting cytokine production in response to ex vivo stimulation in two independent cohorts of 500 and 200 healthy individuals. We demonstrate a strong impact of genetic heritability on cytokine production capacity after challenge with bacterial, fungal, viral, and non-microbial stimuli. In addition to 17 novel genome-wide significant cytokine QTLs (cQTLs), our study provides a comprehensive picture of the genetic variants that influence six different cytokines in whole blood, blood mononuclear cells, and macrophages. Important biological pathways that contain cytokine QTLs map to pattern recognition receptors (TLR1-6-10 cluster), cytokine and complement inhibitors, and the kallikrein system. The cytokine QTLs show enrichment for monocyte-specific enhancers, are more often located in regions under positive selection, and are significantly enriched among SNPs associated with infections and immune-mediated diseases. PAPERCLIP.

Indexed as

AdolescentAdultAgedBloodCytokinesFemaleGenome-Wide Association StudyHuman Genome ProjectHumansInfectionsLeukocytes, MononuclearMacrophagesMaleMiddle AgedPolymorphism, Single NucleotideQuantitative Trait LociCytokinescytokine heritabilitycytokine QTLimmunogenomicsinnate immune response

Identifiers

PMID27814507
OpenAlexW2547161721

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.