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

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 gen...

Full description

Saved in:
Bibliographic Details
Published inFrontiers in immunology Vol. 13; p. 913555
Main Authors Crinzi, Elizabeth A, Haley, Emma K, Poppenberg, Kerry E, Jiang, Kaiyu, Tutino, Vincent M, Jarvis, James N
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 29.09.2022
Subjects
Online AccessGet full text

Cover

Loading…
Abstract 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. 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. 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. These findings support the idea that both innate and adaptive immunity are impacted by JIA genetic risk variants.
AbstractList 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.IntroductionGenome 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.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.Materials and methodsWe 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.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.ResultsThe 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.These findings support the idea that both innate and adaptive immunity are impacted by JIA genetic risk variants.ConclusionsThese findings support the idea that both innate and adaptive immunity are impacted by JIA genetic risk variants.
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. 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. 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. These findings support the idea that both innate and adaptive immunity are impacted by JIA genetic risk variants.
IntroductionGenome 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 methodsWe 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.ResultsThe 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.ConclusionsThese findings support the idea that both innate and adaptive immunity are impacted by JIA genetic risk variants.
Author Haley, Emma K
Tutino, Vincent M
Poppenberg, Kerry E
Crinzi, Elizabeth A
Jarvis, James N
Jiang, Kaiyu
AuthorAffiliation 2 Canon Stroke and Vascular Center, University at Buffalo Jacobs School of Medicine & Biomedical Sciences , Buffalo, NY , United States
3 Department of Neurosurgery, University at Buffalo Jacobs School of Medicine & Biomedical Sciences , Buffalo, NY , United States
1 Department of Pediatrics, University at Buffalo Jacobs School of Medicine & Biomedical Sciences , Buffalo, NY , United States
4 Genetics, Genomics, & Bioinformatics Program, University at Buffalo Jacobs School of Medicine & Biomedical Sciences , Buffalo, NY , United States
AuthorAffiliation_xml – name: 3 Department of Neurosurgery, University at Buffalo Jacobs School of Medicine & Biomedical Sciences , Buffalo, NY , United States
– name: 2 Canon Stroke and Vascular Center, University at Buffalo Jacobs School of Medicine & Biomedical Sciences , Buffalo, NY , United States
– name: 4 Genetics, Genomics, & Bioinformatics Program, University at Buffalo Jacobs School of Medicine & Biomedical Sciences , Buffalo, NY , United States
– name: 1 Department of Pediatrics, University at Buffalo Jacobs School of Medicine & Biomedical Sciences , Buffalo, NY , United States
Author_xml – sequence: 1
  givenname: Elizabeth A
  surname: Crinzi
  fullname: Crinzi, Elizabeth A
  organization: Department of Pediatrics, University at Buffalo Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, United States
– sequence: 2
  givenname: Emma K
  surname: Haley
  fullname: Haley, Emma K
  organization: Department of Pediatrics, University at Buffalo Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, United States
– sequence: 3
  givenname: Kerry E
  surname: Poppenberg
  fullname: Poppenberg, Kerry E
  organization: Department of Neurosurgery, University at Buffalo Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, United States
– sequence: 4
  givenname: Kaiyu
  surname: Jiang
  fullname: Jiang, Kaiyu
  organization: Department of Pediatrics, University at Buffalo Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, United States
– sequence: 5
  givenname: Vincent M
  surname: Tutino
  fullname: Tutino, Vincent M
  organization: Department of Neurosurgery, University at Buffalo Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, United States
– sequence: 6
  givenname: James N
  surname: Jarvis
  fullname: Jarvis, James N
  organization: Genetics, Genomics, & Bioinformatics Program, University at Buffalo Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, United States
BackLink https://www.ncbi.nlm.nih.gov/pubmed/36248892$$D View this record in MEDLINE/PubMed
BookMark eNpVkstu3CAUhq0qVZOmeYBuKpaVqpmYu9lUiqa3SJG6adcIc_EwtcEFHGleIM9dZiaNkrM5iMP_nQP8b5uzEINtmvewXWPciWvnp2lZoxahtYCYUvqquYCMkRVGiJw9W583Vznv2hpEYIzpm-YcM0S6TqCL5uEmqHGffQbRAb1NcVLFB2BUUSAv8xxTyUCBFEcLXExg8wWST2CKIep9sfl6UjrFeasGm0HVTdb4A2AAgw22eA2Sz3-Oyt1yb4OvGG98nFXZ1qJKZZt88fld89qpMdurx3zZ_P729dfmx-ru5_fbzc3dShNGy4phwg2lhPc9ZIQJrLQmCHWOQ-EgpdzytscQdQIa3DFDesdazDixNQkM8WVze-KaqHZyTn5SaS-j8vK4EdMg60xej1ZSrgy2TlHFSA3Tc4OcsR13bd8p1FbW5xNrXvp6b21DSWp8AX1ZCX4rh3gvBaWCd6wCPj4CUvy72Fzk5LO246iCjUuWiCNaOzOG6lF4OlpfO-dk3VMb2MqDHeTRDvJgB3myQ9V8eD7fk-L_5-N_t261jA
CitedBy_id crossref_primary_10_3389_fimmu_2023_1190018
crossref_primary_10_1016_j_xhgg_2024_100277
crossref_primary_10_1097_MD_0000000000037567
crossref_primary_10_3390_genes15040513
Cites_doi 10.1002/art.39135
10.1016/j.ajhg.2018.04.002
10.1186/ar2048
10.1101/2022.03.07.483040
10.1016/j.cell.2019.02.027
10.1038/nmeth.3329
10.1093/nar/gkw500
10.1016/j.cell.2018.07.047
10.1016/j.cell.2016.10.024
10.1038/srep27453
10.1097/BOR.0000000000000637
10.1016/j.cyto.2012.05.003
10.1136/annrheumdis-2020-217470
10.1016/j.molcel.2013.07.010
10.1371/journal.pone.0235857
10.1002/art.40727
10.1016/j.molcel.2017.08.006
10.1186/s13075-017-1260-x
10.1189/jlb.0306170
10.1038/s41467-021-21854-5
10.1186/s13075-015-0723-1
10.1038/nrrheum.2011.68
10.1016/j.cell.2016.04.027
10.1016/j.cels.2015.07.012
10.1016/j.jaut.2015.08.002
10.3390/ijms22157960
10.1093/bioinformatics/btu779
10.1002/art.27424
10.1186/s13075-016-1059-1
10.1172/jci.insight.121544
10.1038/nri3671
10.1002/art.24450
10.1136/annrheumdis-2016-210025
10.1038/s41584-021-00590-6
10.1097/bor.0000000000000526
10.1002/art.39694
10.1097/00002281-200009000-00012
10.1038/s41467-018-05328-9
10.1002/1529-0131(200008)43:8<1858::AID-ANR23>3.0.CO;2-A
10.1136/annrheumdis-2012-201329
10.1186/s12920-021-00964-5
10.1186/s12920-019-0591-7
10.1016/j.autrev.2011.02.001
10.1038/ng.2614
10.1002/art.40216
ContentType Journal Article
Copyright Copyright © 2022 Crinzi, Haley, Poppenberg, Jiang, Tutino and Jarvis.
Copyright © 2022 Crinzi, Haley, Poppenberg, Jiang, Tutino and Jarvis 2022 Crinzi, Haley, Poppenberg, Jiang, Tutino and Jarvis
Copyright_xml – notice: Copyright © 2022 Crinzi, Haley, Poppenberg, Jiang, Tutino and Jarvis.
– notice: Copyright © 2022 Crinzi, Haley, Poppenberg, Jiang, Tutino and Jarvis 2022 Crinzi, Haley, Poppenberg, Jiang, Tutino and Jarvis
DBID CGR
CUY
CVF
ECM
EIF
NPM
AAYXX
CITATION
7X8
5PM
DOA
DOI 10.3389/fimmu.2022.913555
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
CrossRef
MEDLINE - Academic
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
CrossRef
MEDLINE - Academic
DatabaseTitleList MEDLINE - Academic
MEDLINE

Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 3
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Biology
EISSN 1664-3224
ExternalDocumentID oai_doaj_org_article_57ad3efa5a64444db7d2fde87f0b8a20
10_3389_fimmu_2022_913555
36248892
Genre Research Support, Non-U.S. Gov't
Journal Article
Research Support, N.I.H., Extramural
GrantInformation_xml – fundername: NIAMS NIH HHS
  grantid: R21 AR071878
– fundername: NIAMS NIH HHS
  grantid: R21 AR076948
– fundername: NCATS NIH HHS
  grantid: UL1 TR001412
– fundername: ;
GroupedDBID 53G
5VS
9T4
AAFWJ
AAKDD
ACGFO
ACGFS
ACXDI
ADBBV
ADRAZ
AENEX
AFPKN
ALMA_UNASSIGNED_HOLDINGS
AOIJS
BAWUL
BCNDV
CGR
CUY
CVF
DIK
EBS
ECM
EIF
EMOBN
GROUPED_DOAJ
GX1
HYE
IAO
IEA
IHR
IHW
IPNFZ
KQ8
M48
M~E
NPM
OK1
PGMZT
RIG
RNS
RPM
AAYXX
CITATION
7X8
5PM
ID FETCH-LOGICAL-c465t-6347d5547bb164693acc4228f719f1557e70b312891d386d4bf603674e6039313
IEDL.DBID RPM
ISSN 1664-3224
IngestDate Tue Oct 22 15:12:01 EDT 2024
Tue Sep 17 21:31:01 EDT 2024
Sat Oct 26 04:07:37 EDT 2024
Thu Nov 21 21:22:35 EST 2024
Sat Nov 02 12:23:59 EDT 2024
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Keywords causal variant
juvenile arthritis
genetics
haplotype
enhancers
macrophage
monocyte
Language English
License Copyright © 2022 Crinzi, Haley, Poppenberg, Jiang, Tutino and Jarvis.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c465t-6347d5547bb164693acc4228f719f1557e70b312891d386d4bf603674e6039313
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Edited by: Janine Lamb, The University of Manchester, United Kingdom
This article was submitted to Autoimmune and Autoinflammatory Disorders, a section of the journal Frontiers in Immunology
Reviewed by: Paul Martin, The University of Manchester, United Kingdom; Matteo Vecellio, University of Oxford, United Kingdom
OpenAccessLink https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9559786/
PMID 36248892
PQID 2725444662
PQPubID 23479
ParticipantIDs doaj_primary_oai_doaj_org_article_57ad3efa5a64444db7d2fde87f0b8a20
pubmedcentral_primary_oai_pubmedcentral_nih_gov_9559786
proquest_miscellaneous_2725444662
crossref_primary_10_3389_fimmu_2022_913555
pubmed_primary_36248892
PublicationCentury 2000
PublicationDate 2022-09-29
PublicationDateYYYYMMDD 2022-09-29
PublicationDate_xml – month: 09
  year: 2022
  text: 2022-09-29
  day: 29
PublicationDecade 2020
PublicationPlace Switzerland
PublicationPlace_xml – name: Switzerland
PublicationTitle Frontiers in immunology
PublicationTitleAlternate Front Immunol
PublicationYear 2022
Publisher Frontiers Media S.A
Publisher_xml – name: Frontiers Media S.A
References Hnisz (B28) 2016; 167
Throm (B33) 2018; 3
Durand (B27) 2016; 3
Phanstiel (B26) 2017; 67
Wu (B15) 2021; 22
Jarvis (B11) 2009; 60
Herlin (B2) 2014; 1
Hollenbach (B18) 2010; 62
Heinz (B29) 2018; 174
Jiang (B14) 2016; 18
Pelikan (B36) 2012; 71
Mellins (B40) 2011; 7
Shimizu (B44) 2012; 60
Yasin (B41) 2018; 30
Zhu (B7) 2017; 19
Danko (B23) 2015; 12
Gasperini (B25) 2019; 176
Hinks (B3) 2013; 45
Hinks (B17) 2017; 76
McIntosh (B4) 2017; 69
Hersh (B1) 2015; 64
Foell (B37) 2007; 81
Brodie (B38) 2016; 44
Anink (B12) 2015; 17
Nigrovic (B20) 2021; 17
Gallagher (B5) 2018; 102
Jiang (B8) 2020; 15
Jiang (B32) 2022
Pelikan (B39) 2018; 9
Jarvis (B10) 2006; 8
Guillaume (B16) 2000; 43
Lin (B42) 2011; 10
Jiang (B6) 2015; 67
Grom (B9) 2000; 12
Hu (B35) 2016; 6
Lu (B46) 2021; 12
Tewhey (B31) 2016; 165
Hinze (B13) 2019; 71
Ginhoux (B45) 2014; 14
Kaikkonen (B24) 2013; 51
Arnold (B21) 2015; 31
Nigrovic (B19) 2019; 31
Poppenberg (B22) 2021; 14
Schulert (B30) 2021; 80
Poppenberg (B34) 2019; 12
Schulert (B43) 2016; 68
References_xml – volume: 67
  year: 2015
  ident: B6
  article-title: Disease-associated single-nucleotide polymorphisms from noncoding regions in juvenile idiopathic arthritis are located within or adjacent to functional genomic elements of human neutrophils and Cd4+ T cells
  publication-title: Arthritis Rheumatol
  doi: 10.1002/art.39135
  contributor:
    fullname: Jiang
– volume: 102
  year: 2018
  ident: B5
  article-title: The post-gwas era: From association to function
  publication-title: Am J Hum Genet
  doi: 10.1016/j.ajhg.2018.04.002
  contributor:
    fullname: Gallagher
– volume: 8
  start-page: R154
  year: 2006
  ident: B10
  article-title: Evidence for chronic, peripheral activation of neutrophils in polyarticular juvenile rheumatoid arthritis
  publication-title: Arthritis Res Ther
  doi: 10.1186/ar2048
  contributor:
    fullname: Jarvis
– year: 2022
  ident: B32
  article-title: A systematic strategy for identifying causal single nucleotide polymorphisms and their target genes on juvenile arthritis risk haplotypes
  publication-title: bioRxiv
  doi: 10.1101/2022.03.07.483040
  contributor:
    fullname: Jiang
– volume: 176
  start-page: 1516
  year: 2019
  ident: B25
  article-title: A genome-wide framework for mapping gene regulation Via cellular genetic screens
  publication-title: Cell
  doi: 10.1016/j.cell.2019.02.027
  contributor:
    fullname: Gasperini
– volume: 12
  year: 2015
  ident: B23
  article-title: Identification of active transcriptional regulatory elements from gro-seq data
  publication-title: Nat Methods
  doi: 10.1038/nmeth.3329
  contributor:
    fullname: Danko
– volume: 44
  year: 2016
  ident: B38
  article-title: How far from the snp may the causative genes be
  publication-title: Nucleic Acids Res
  doi: 10.1093/nar/gkw500
  contributor:
    fullname: Brodie
– volume: 174
  start-page: 1522
  year: 2018
  ident: B29
  article-title: Transcription elongation can affect genome 3d structure
  publication-title: Cell
  doi: 10.1016/j.cell.2018.07.047
  contributor:
    fullname: Heinz
– volume: 167
  year: 2016
  ident: B28
  article-title: Insulated neighborhoods: Structural and functional units of mammalian gene control
  publication-title: Cell
  doi: 10.1016/j.cell.2016.10.024
  contributor:
    fullname: Hnisz
– volume: 6
  year: 2016
  ident: B35
  article-title: Complexity and specificity of the neutrophil transcriptomes in juvenile idiopathic arthritis
  publication-title: Sci Rep
  doi: 10.1038/srep27453
  contributor:
    fullname: Hu
– volume: 31
  year: 2019
  ident: B19
  article-title: Implications of juvenile idiopathic arthritis genetic risk variants for disease pathogenesis and classification
  publication-title: Curr Opin Rheumatol
  doi: 10.1097/BOR.0000000000000637
  contributor:
    fullname: Nigrovic
– volume: 60
  year: 2012
  ident: B44
  article-title: Compensated inflammation in systemic juvenile idiopathic arthritis: Role of alternatively activated macrophages
  publication-title: Cytokine
  doi: 10.1016/j.cyto.2012.05.003
  contributor:
    fullname: Shimizu
– volume: 80
  year: 2021
  ident: B30
  article-title: Monocyte and bone marrow macrophage transcriptional phenotypes in systemic juvenile idiopathic arthritis reveal Trim8 as a mediator of ifn-Γ hyper-responsiveness and risk for macrophage activation syndrome
  publication-title: Ann Rheum Dis
  doi: 10.1136/annrheumdis-2020-217470
  contributor:
    fullname: Schulert
– volume: 51
  year: 2013
  ident: B24
  article-title: Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription
  publication-title: Mol Cell
  doi: 10.1016/j.molcel.2013.07.010
  contributor:
    fullname: Kaikkonen
– volume: 15
  year: 2020
  ident: B8
  article-title: Broadening our understanding of the genetics of juvenile idiopathic arthritis (Jia): Interrogation of three dimensional chromatin structures and genetic regulatory elements within jia-associated risk loci
  publication-title: PloS One
  doi: 10.1371/journal.pone.0235857
  contributor:
    fullname: Jiang
– volume: 71
  year: 2019
  ident: B13
  article-title: Serum S100a8/A9 and S100a12 levels in children with polyarticular forms of juvenile idiopathic arthritis: Relationship to maintenance of clinically inactive disease during anti-tumor necrosis factor therapy and occurrence of disease flare after discontinuation of therapy
  publication-title: Arthritis Rheumatol
  doi: 10.1002/art.40727
  contributor:
    fullname: Hinze
– volume: 67
  start-page: 1037
  year: 2017
  ident: B26
  article-title: Static and dynamic DNA loops form ap-1-Bound activation hubs during macrophage development
  publication-title: Mol Cell
  doi: 10.1016/j.molcel.2017.08.006
  contributor:
    fullname: Phanstiel
– volume: 19
  start-page: 57
  year: 2017
  ident: B7
  article-title: Chromatin landscapes and genetic risk for juvenile idiopathic arthritis
  publication-title: Arthritis Res Ther
  doi: 10.1186/s13075-017-1260-x
  contributor:
    fullname: Zhu
– volume: 81
  start-page: 28
  year: 2007
  ident: B37
  article-title: S100 proteins expressed in phagocytes: a novel group of damage-associated molecular pattern molecules
  publication-title: J Leukocyte Biol
  doi: 10.1189/jlb.0306170
  contributor:
    fullname: Foell
– volume: 12
  start-page: 1611
  year: 2021
  ident: B46
  article-title: Global discovery of lupus genetic risk variant allelic enhancer activity
  publication-title: Nat Commun
  doi: 10.1038/s41467-021-21854-5
  contributor:
    fullname: Lu
– volume: 17
  start-page: 200
  year: 2015
  ident: B12
  article-title: Mrp8/14 serum levels as a predictor of response to starting and stopping anti-tnf treatment in juvenile idiopathic arthritis
  publication-title: Arthritis Res Ther
  doi: 10.1186/s13075-015-0723-1
  contributor:
    fullname: Anink
– volume: 7
  year: 2011
  ident: B40
  article-title: Pathogenesis of systemic juvenile idiopathic arthritis: Some answers, more questions
  publication-title: Nat Rev Rheumatol
  doi: 10.1038/nrrheum.2011.68
  contributor:
    fullname: Mellins
– volume: 165
  year: 2016
  ident: B31
  article-title: Direct identification of hundreds of expression-modulating variants using a multiplexed reporter assay
  publication-title: Cell
  doi: 10.1016/j.cell.2016.04.027
  contributor:
    fullname: Tewhey
– volume: 3
  start-page: 99
  year: 2016
  ident: B27
  article-title: Juicebox provides a visualization system for Hi-c contact maps with unlimited zoom
  publication-title: Cell Syst
  doi: 10.1016/j.cels.2015.07.012
  contributor:
    fullname: Durand
– volume: 64
  year: 2015
  ident: B1
  article-title: Immunogenetics of juvenile idiopathic arthritis: A comprehensive review
  publication-title: J Autoimmun
  doi: 10.1016/j.jaut.2015.08.002
  contributor:
    fullname: Hersh
– volume: 1
  start-page: 73
  year: 2014
  ident: B2
  article-title: Update on genetic susceptibility and pathogenesis in juvenile idiopathic arthritis
  publication-title: Eur Med J Rheumatol
  contributor:
    fullname: Herlin
– volume: 22
  year: 2021
  ident: B15
  article-title: Signals and mechanisms regulating monocyte and macrophage activation in the pathogenesis of juvenile idiopathic arthritis
  publication-title: Int J Mol Sci
  doi: 10.3390/ijms22157960
  contributor:
    fullname: Wu
– volume: 31
  year: 2015
  ident: B21
  article-title: Snipa: An interactive, genetic variant-centered annotation browser
  publication-title: Bioinformatics
  doi: 10.1093/bioinformatics/btu779
  contributor:
    fullname: Arnold
– volume: 62
  year: 2010
  ident: B18
  article-title: Juvenile idiopathic arthritis and hla class I and class ii interactions and age-at-Onset effects
  publication-title: Arthritis Rheum
  doi: 10.1002/art.27424
  contributor:
    fullname: Hollenbach
– volume: 18
  start-page: 157
  year: 2016
  ident: B14
  article-title: Whole blood expression profiling from the treat trial: Insights for the pathogenesis of polyarticular juvenile idiopathic arthritis
  publication-title: Arthritis Res Ther
  doi: 10.1186/s13075-016-1059-1
  contributor:
    fullname: Jiang
– volume: 3
  year: 2018
  ident: B33
  article-title: Identification of enhanced ifn-Γ signaling in polyarticular juvenile idiopathic arthritis with mass cytometry
  publication-title: JCI Insight
  doi: 10.1172/jci.insight.121544
  contributor:
    fullname: Throm
– volume: 14
  start-page: 392
  year: 2014
  ident: B45
  article-title: Monocytes and macrophages: Developmental pathways and tissue homeostasis
  publication-title: Nat Rev Immunol
  doi: 10.1038/nri3671
  contributor:
    fullname: Ginhoux
– volume: 60
  year: 2009
  ident: B11
  article-title: Gene expression profiling in neutrophils from children with polyarticular juvenile idiopathic arthritis
  publication-title: Arthritis Rheum
  doi: 10.1002/art.24450
  contributor:
    fullname: Jarvis
– volume: 76
  year: 2017
  ident: B17
  article-title: Fine-mapping the mhc locus in juvenile idiopathic arthritis (Jia) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases
  publication-title: Ann Rheum Dis
  doi: 10.1136/annrheumdis-2016-210025
  contributor:
    fullname: Hinks
– volume: 17
  year: 2021
  ident: B20
  article-title: Biological classification of childhood arthritis: Roadmap to a molecular nomenclature
  publication-title: Nat Rev Rheumatol
  doi: 10.1038/s41584-021-00590-6
  contributor:
    fullname: Nigrovic
– volume: 30
  year: 2018
  ident: B41
  article-title: Systemic juvenile idiopathic arthritis and macrophage activation syndrome: Update on pathogenesis and treatment
  publication-title: Curr Opin Rheumatol
  doi: 10.1097/bor.0000000000000526
  contributor:
    fullname: Yasin
– volume: 68
  year: 2016
  ident: B43
  article-title: Monocyte microrna expression in active systemic juvenile idiopathic arthritis implicates microrna-125a-5p in polarized monocyte phenotypes
  publication-title: Arthritis Rheumatol
  doi: 10.1002/art.39694
  contributor:
    fullname: Schulert
– volume: 12
  year: 2000
  ident: B9
  article-title: T-Cell and T-cell receptor abnormalities in the immunopathogenesis of juvenile rheumatoid arthritis
  publication-title: Curr Opin Rheumatol
  doi: 10.1097/00002281-200009000-00012
  contributor:
    fullname: Grom
– volume: 9
  start-page: 2905
  year: 2018
  ident: B39
  article-title: Enhancer histone-qtls are enriched on autoimmune risk haplotypes and influence gene expression within chromatin networks
  publication-title: Nat Commun
  doi: 10.1038/s41467-018-05328-9
  contributor:
    fullname: Pelikan
– volume: 43
  year: 2000
  ident: B16
  article-title: Long-term outcome and prognosis in oligoarticular-onset juvenile idiopathic arthritis
  publication-title: Arthritis Rheum
  doi: 10.1002/1529-0131(200008)43:8<1858::AID-ANR23>3.0.CO;2-A
  contributor:
    fullname: Guillaume
– volume: 71
  year: 2012
  ident: B36
  article-title: Phagocyte-specific S100 proteins and high-sensitivity c reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis: a comparative study
  publication-title: Ann Rheum Dis
  doi: 10.1136/annrheumdis-2012-201329
  contributor:
    fullname: Pelikan
– volume: 14
  start-page: 114
  year: 2021
  ident: B22
  article-title: Broadening our understanding of genetic risk for Scleroderma/Systemic sclerosis by querying the chromatin architecture surrounding the risk haplotypes
  publication-title: BMC Med Genomics
  doi: 10.1186/s12920-021-00964-5
  contributor:
    fullname: Poppenberg
– volume: 12
  start-page: 149
  year: 2019
  ident: B34
  article-title: Epigenetic landscapes suggest that genetic risk for intracranial aneurysm operates on the endothelium
  publication-title: BMC Med Genomics
  doi: 10.1186/s12920-019-0591-7
  contributor:
    fullname: Poppenberg
– volume: 10
  year: 2011
  ident: B42
  article-title: The pathogenesis of Oligoarticular/Polyarticular vs systemic juvenile idiopathic arthritis
  publication-title: Autoimmun Rev
  doi: 10.1016/j.autrev.2011.02.001
  contributor:
    fullname: Lin
– volume: 45
  year: 2013
  ident: B3
  article-title: Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis
  publication-title: Nat Genet
  doi: 10.1038/ng.2614
  contributor:
    fullname: Hinks
– volume: 69
  year: 2017
  ident: B4
  article-title: Genome-wide association meta-analysis reveals novel juvenile idiopathic arthritis susceptibility loci
  publication-title: Arthritis Rheumatol
  doi: 10.1002/art.40216
  contributor:
    fullname: McIntosh
SSID ssj0000493335
Score 2.3918226
Snippet Genome wide association studies (GWAS) have identified multiple regions that confer genetic risk for the polyarticular/oligoarticular forms of juvenile...
IntroductionGenome wide association studies (GWAS) have identified multiple regions that confer genetic risk for the polyarticular/oligoarticular forms of...
SourceID doaj
pubmedcentral
proquest
crossref
pubmed
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
StartPage 913555
SubjectTerms Arthritis, Juvenile - genetics
causal variant
Chromatin - genetics
genetics
Genome-Wide Association Study
haplotype
Humans
Immunology
juvenile arthritis
Lipopolysaccharide Receptors - immunology
macrophage
Macrophages
monocyte
Monocytes
SummonAdditionalLinks – databaseName: DOAJ Directory of Open Access Journals
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3LatwwFBUlUOim9N3pCwW6anFjPSxZyyZtCIF21UB2Qk9mAmOHzHiRH-h3915pJsyUQDfdjsdY6FzrnmsdnUvIR8jRwXsmGt0m38jOm8b1RWWFZmyMs-jwO-SPn-rsQp5fdpc7rb5QE1btgevEQcHuokjZdQ4yt5TR68hzTL3Ore8dr9V6y3eKqavKe4UQXd3GhCrMHOXFcjlBPcj5F8MgyXZ7iaj49d9HMv_WSu4kn9Mn5PGGNdKvdbRPyYM0PCMPax_J2-fk99ZahI6ZhvnNiDR0oKj-pKvpuuwKUEdRSUiBpNKTb0x-phCAY7gFqnm0dNjIaw5Ly4rCfeU0CcqhKUQXHnKkKEAvd15NsDjCQkIXcTGWbsaBwhzOizXSC3Jx-v3XyVmzabDQBKm6daOE1BH4hAa0FNTJwoWAlmBZM5OBaOikWy8ggxkWRa-i9FlBxtMyKTzSy8RLcjCMQ3qNCqmeJdX5kL0HjtCb5FvnBW-N587rMCOftrNtr6uPhoX6A6GxBRqL0NgKzYwcIx53f0QL7PIDBIbdBIb9V2DMyOEWTQuvDO6DuCGN08pyjb5sUik-I68qunePgnwOS5qBK3oP972x7F8ZFvNiy128_Hr15n8M_i15hPOBwhRu3pGD9c2U3gP7WfsPJdD_AKW1Bfo
  priority: 102
  providerName: Directory of Open Access Journals
– databaseName: Scholars Portal Journals: Open Access(OpenAccess)
  dbid: M48
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3LjtMwFLWGQUhsEG_KS0ZiBcpM_IidLBCCgdEIaVhRaXaWn7QjmgxtI9Ef4Lu510lHFHXBtmkezbn2Pbc-PpeQ15CjvXNMFLqMrpCVawpbZ5UVmrExzoLF_yHPv6qzqfxyUV0ckG17q_EFrvaWdthParr8cfTr5-Y9DPh3WHFCvj1O88Wih1KP86OGQf6sbpCbHBIjKrzOR7Z_OZBhIXLLTaaULCCU5bDOuf8qO5kqG_rvY6H_iin_yk6nd8mdkVbSD0Mc3CMHsb1Pbg2NJjcPyO-t9wjtEvWzZYc8taUoD6Wr_iovG1BLUWpIgcXSk09MvqUQoZ3fABc9Xljs9DWDuWdF4by83QT10hTCD3dBUlSo5zMve5g9Yaah8zDvcrtjTyE6Z9k76SGZnn7-dnJWjB0YCi9VtS6UkDoA4dAAp4JCWljv0TMsadYkYCI66tIJSHENC6JWQbqkICVqGRXu-WXiETlsuzY-QQlVzaKqnE_OAYmom-hK6wQvG8et035C3mzftrkajDYMFCgIjcnQGITGDNBMyEfE4_qL6JGdP-iW38045EylbRAx2coC55MyOB14CrHWqXS15eWEvNqiaWBM4UKJbWPXrwzXaNwmleIT8nhA9_pWkPBhzmvgiN7BfedZdo-081n27c5mf7V6-h_3fUZu489FYQpvnpPD9bKPL4D9rN3LHNN_AK0lBBg
  priority: 102
  providerName: Scholars Portal
Title Analysis of chromatin data supports a role for CD14+ monocytes/macrophages in mediating genetic risk for juvenile idiopathic arthritis
URI https://www.ncbi.nlm.nih.gov/pubmed/36248892
https://www.proquest.com/docview/2725444662
https://pubmed.ncbi.nlm.nih.gov/PMC9559786
https://doaj.org/article/57ad3efa5a64444db7d2fde87f0b8a20
Volume 13
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Nb9QwELXaSkhcEJSvpbQyEidQNvFH7ORIF0qFtIgDlfYW2Y7DpmqS1e7m0D_Q382Ms6m6iFMvOSSxEvlNPG_i52dCPkKOdtYyEenE20imNo9MFlRWaMbGOCsN_oec_1SXV_LHIl0ckHRcCxNE-87W0_ammbb1MmgrV42LR51Y_Gs-C65pmYoPySGk3wcl-vVAeYUQ6TCDCQVYHld10_RQCnI-zRnk13QvBwWr_v_xy39lkg_yzsVz8mxHGOmX4cVekAPfHpMnwxaSty_J3egqQruKuuW6QwbaUhR-0k2_ChMC1FAUEVLgp3T2lcnPFGKvc7fAMuPG4B5eSxhVNhTahYUkqISmEFi4vpGi9jy0vO5hXIQxhNZl3YWNjB2F7loGV6RX5Ori2-_ZZbTbWyFyUqXbSAmpS6ASGoBSUCIL4xy6gVWa5RVwDO11YgUkr5yVIlOltJWCZKelV7ial4nX5KjtWv8WxVEZ8yq1rrIW6EGWe5sYK3iSW26sdhPyaeztYjVYaBRQeiA0RYCmQGiKAZoJOUc87m9E9-twolv_KXYxUKTalMJXJjXA5qQsrS55VfpMV4nNDE8m5MOIZgFfC06BmNZ3_abgGi3ZpFJ8Qt4M6N4_ClI5jGY5XNF7uO-9y_4VCNDgyL0LyHePbnlCnmInoBCF5-_J0Xbd-1NgO1t7Fv4SwPH7gsFxLrOzEO9_ARZtBnQ
link.rule.ids 230,314,727,780,784,864,885,2102,24318,27924,27925,53791,53793
linkProvider National Library of Medicine
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3LbtQwFLVKEYIN4s3wNBIrUCaJn_ESBqoBOhWLVurOsh2nk4oko5nJoj_Ad3PtTKoOYsU2jpXI58b33Pj4GKH3kKOdtTlNZOZtwrhViSmiyiqYseUkL034D7k4EfMz9v2cnx8gPu6FiaJ9Z-tp-6uZtvUyaitXjUtHnVj6czGLrmmFSG-h25xKld8o0i8H0ksp5cMaJpRgKq3qpumhGCRkqnLIsHwvC0Wz_n8xzL-Fkjcyz9EDdH9HGfGn4dUeogPfPkJ3hkMkrx6j36OvCO4q7JbrLnDQFgfpJ970q7gkgA0OMkIMDBXPvuTsI4bo69wV8My0MeEUryXMKxsM_eJWkqCFxhBaYYcjDurz2POyh5kRZhFcl3UXjzJ2GAZsGX2RnqCzo6-ns3myO10hcUzwbSIokyWQCQlQCSiSqXEu-IFVMlcVsAzpZWYppC-Vl7QQJbOVgHQnmRdhP29On6LDtmv98yCPKnIvuHWVtUAQCuVtZiwlmbLEWOkm6MM42no1mGhoKD4CNDpCowM0eoBmgj4HPK5vDP7X8UK3vtC7KNBcmpL6ynADfI6x0sqSVKUvZJXZwpBsgt6NaGr4XsIiiGl91280kcGUjQlBJujZgO71oyCZw3ymoEXu4b73LvstEKLRk3sXki_-u-dbdHd-ujjWx99OfrxE98KABFkKUa_Q4Xbd-9fAfbb2TYz0P4KHBwk
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3LjtMwFLVgEGg2iDcdXkZiBUqT2I6dLKFDNTxmNAtGmp3lV2hGJKn6WMwP8N3c67SjFrFi29RJ5HPre259fC4h7yBHO2tznqgs2EQUtkpMGVVWaMaWs9wb_B_y9EyeXIivl8XlTquvKNp3thl3v9px18yitnLeunSrE0vPTyfRNa2U6dzX6W1yp-Bw351C_WogvpzzYtjHhDKsSuumbddQEDI2rnLIssVeJoqG_f9imX-LJXeyz_QBub-hjfTj8HoPya3QPSJ3h0aS14_J7623CO1r6maLHnloR1H-SZfredwWoIailJACS6WT41x8oBCBvbsGrpm2Bjt5zWBtWVIYF4-ToB6aQnjhKUeKCvQ48moNqyOsJLTxTR_bGTsKkzaL3khPyMX084_JSbLpsJA4IYtVIrlQHgiFArgkFMrcOIeeYLXKqxqYhgoqsxxSWJV7XkovbC0h5SkRJJ7pzflTctD1XXiOEqkyD7KwrrYWSEJZBZsZy1lWWWasciPyfjvbej4YaWgoQBAaHaHRCI0eoBmRT4jHzRfRAzt-0C9-6k0k6EIZz0NtCgOcTghvlWe1D6WqM1salo3I2y2aGn4zuBFiutCvl5opNGYTUrIReTage_MoSOiwplVwRe3hvvcu-1cgTKMv9yYsj_575Bty7_x4qr9_Ofv2ghzifKAyhVUvycFqsQ6vgP6s7OsY6H8AM6kIHA
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Analysis+of+chromatin+data+supports+a+role+for+CD14%2B+monocytes%2Fmacrophages+in+mediating+genetic+risk+for+juvenile+idiopathic+arthritis&rft.jtitle=Frontiers+in+immunology&rft.au=Crinzi%2C+Elizabeth+A&rft.au=Haley%2C+Emma+K&rft.au=Poppenberg%2C+Kerry+E&rft.au=Jiang%2C+Kaiyu&rft.date=2022-09-29&rft.issn=1664-3224&rft.eissn=1664-3224&rft.volume=13&rft.spage=913555&rft_id=info:doi/10.3389%2Ffimmu.2022.913555&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1664-3224&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1664-3224&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1664-3224&client=summon