Evidence map›Paper›PMID 36248892›Full record

ArticleFrontiers in immunology2022

Analysis of chromatin data supports a role for CD14+ monocytes/macrophages in mediating genetic risk for juvenile idiopathic arthritis.

Elizabeth A Crinzi, Emma K Haley, Kerry E Poppenberg, Kaiyu Jiang, Vincent M Tutino, James N Jarvis

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.6field-weighted citation impact, top 15% 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

4 citing papers in PubMed, 10 citations in OpenAlex.

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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 1 country.

Elizabeth A CrinziDepartment of Pediatrics, University at Buffalo Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, United States.
Emma K HaleyDepartment of Pediatrics, University at Buffalo Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, United States.
Kerry E PoppenbergCanon Stroke and Vascular Center, University at Buffalo Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, United States.
Kaiyu JiangDepartment of Pediatrics, University at Buffalo Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, United States.
Vincent M TutinoCanon Stroke and Vascular Center, University at Buffalo Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, United States.
James N JarvisDepartment of Pediatrics, University at Buffalo Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, United States.
Jacobs (United States) · USUniversity at Buffalo, State University of New York · US

Funding

University of Buffalo Clinical and Translational Science Institute - Supplement SchulyerUL1TR001412 · NCATS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MURPHY, TIMOTHY F · 2015 to 2024
$33.8M
Identifying Causal Variants in Juvenile Arthritis Using a Massively Parallel Reporter AssayR21AR071878 · NIAMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI JARVIS, JAMES N · 2018 to 2019
$386k
Using Chromatin Architecture to Develop of Therapeutic Pipeline for Juvenile ArthritisR21AR076948 · NIAMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI JARVIS, JAMES N · 2020 to 2021
$381k
NCATS NIH HHS UL1 TR001412NIAMS NIH HHS R21 AR071878NIAMS NIH HHS R21 AR076948
6 · The paper itself

Abstract

Introduction: Genome wide association studies (GWAS) have identified multiple regions that confer genetic risk for the polyarticular/oligoarticular forms of juvenile idiopathic arthritis (JIA). However, genome-wide scans do not identify the cells impacted by genetic polymorphisms on the risk haplotypes or the genes impacted by those variants. We have shown that genetic variants driving JIA risk are likely to affect both innate and adaptive immune functions. We provide additional evidence that JIA risk variants impact innate immunity. Materials and methods: We queried publicly available H3K4me1/H3K27ac ChIP-seq data in CD14+ monocytes to determine whether the linkage disequilibrium (LD) blocks incorporating the SNPs that tag JIA risk loci showed enrichment for these epigenetic marks. We also queried monocyte/macrophage GROseq data, a functional readout of active enhancers. We defined the topologically associated domains (TADs) encompassing enhancers on the risk haplotypes and identified genes within those TADs expressed in monocytes. We performed ontology analyses of these genes to identify cellular processes that may be impacted by these variants. We also used whole blood RNAseq data from the Genotype-Tissue Expression (GTEx) data base to determine whether SNPs lying within monocyte GROseq peaks influence plausible target genes within the TADs encompassing the JIA risk haplotypes. Results: The LD blocks encompassing the JIA genetic risk regions were enriched for H3K4me1/H3K27ac ChIPseq peaks (p=0.00021 and p=0.022) when compared to genome background. Eleven and sixteen JIA were enriched for resting and activated macrophage GROseq peaks, respectively risk regions (p=0.04385 and p=0.00004). We identified 321 expressed genes within the TADs encompassing the JIA haplotypes in human monocytes. Ontological analysis of these genes showed enrichment for multiple immune functions. Finally, we found that SNPs lying within the GROseq peaks are strongly associated with expression levels of plausible target genes in human whole blood. Conclusions: These findings support the idea that both innate and adaptive immunity are impacted by JIA genetic risk variants.

Indexed as

Arthritis, JuvenileGenome-Wide Association StudyChromatinHumansLipopolysaccharide ReceptorsMacrophagesMonocytesChromatinLipopolysaccharide Receptorscausal variantenhancersgeneticshaplotypejuvenile arthritismacrophagemonocyte

Identifiers

PMID36248892
PMCPMC9559786
OpenAlexW4298005887

What OpenQuestion holds

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LicenceCC BY
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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.