Chromatin activity at GWAS loci identifies T cell states driving complex immune diseases.


Journal

Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904

Informations de publication

Date de publication:
10 2019
Historique:
received: 14 02 2019
accepted: 30 07 2019
pubmed: 25 9 2019
medline: 23 1 2020
entrez: 25 9 2019
Statut: ppublish

Résumé

Immune-disease-associated variants are enriched in active chromatin regions of T cells and macrophages. However, whether these variants function in specific cell states is unknown. Here we stimulated T cells and macrophages in the presence of 13 cytokines and profiled active and open chromatin regions. T cell activation induced major chromatin remodeling, while the presence of cytokines fine-tuned the magnitude of changes. We developed a statistical method that accounts for subtle changes in the chromatin landscape to identify SNP enrichment across cell states. Our results point towards the role of immune-disease-associated variants in early rather than late activation of memory CD4

Identifiants

pubmed: 31548716
doi: 10.1038/s41588-019-0493-9
pii: 10.1038/s41588-019-0493-9
pmc: PMC6872452
mid: EMS83888
doi:

Substances chimiques

Chromatin 0
Cytokines 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1486-1493

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206194
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N014995/1
Pays : United Kingdom

Références

Cell. 2016 Nov 17;167(5):1398-1414.e24
pubmed: 27863251
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Glia. 2016 Apr;64(4):553-69
pubmed: 26649511
Nat Genet. 2017 Dec;49(12):1752-1757
pubmed: 29083406
Science. 2012 Sep 7;337(6099):1190-5
pubmed: 22955828
Nat Commun. 2017 May 24;8:15382
pubmed: 28537254
Nature. 2012 Nov 1;491(7422):119-24
pubmed: 23128233
Nat Genet. 2019 Oct;51(10):1494-1505
pubmed: 31570894
Immunity. 1995 Nov;3(5):541-7
pubmed: 7584144
Nat Rev Rheumatol. 2016 Jan;12(1):63-8
pubmed: 26656659
Nat Med. 2014 Dec;20(12):1410-1416
pubmed: 25329329
Bioinformatics. 2010 Mar 1;26(5):589-95
pubmed: 20080505
Nat Genet. 2013 Nov;45(11):1353-60
pubmed: 24076602
Science. 2017 Mar 31;355(6332):
pubmed: 28360266
F1000Prime Rep. 2014 Mar 03;6:13
pubmed: 24669294
Iran J Immunol. 2013 Mar;10(1):47-54
pubmed: 23502338
Genome Biol. 2014;15(12):550
pubmed: 25516281
BMC Bioinformatics. 2014 Jun 12;15:182
pubmed: 24925680
Nat Genet. 2015 Apr;47(4):381-6
pubmed: 25751624
Nat Genet. 2018 Jan;50(1):42-53
pubmed: 29273806
J Neuroinflammation. 2017 Jul 24;14(1):144
pubmed: 28738904
Nat Commun. 2017 Jul 17;8:16021
pubmed: 28714469
Nature. 2014 Feb 20;506(7488):376-81
pubmed: 24390342
Nat Genet. 2018 Mar;50(3):401-413
pubmed: 29507422
Nat Genet. 2016 Oct;48(10):1193-203
pubmed: 27526324
Genes Immun. 2020 Dec;21(6-8):390-408
pubmed: 33223527
Am J Hum Genet. 2014 Apr 3;94(4):559-73
pubmed: 24702953
Nat Genet. 2011 Nov 06;43(12):1193-201
pubmed: 22057235
Nat Rev Immunol. 2002 May;2(5):364-71
pubmed: 12033742
Nat Genet. 2013 Feb;45(2):124-30
pubmed: 23263488
Am J Hum Genet. 2011 Oct 7;89(4):496-506
pubmed: 21963258
Nat Med. 2013 Jul;19(7):822-4
pubmed: 23836224
Genes Dev. 2017 Mar 1;31(5):451-462
pubmed: 28356342
Am J Hum Genet. 2017 Nov 2;101(5):686-699
pubmed: 29106824
Nat Genet. 2017 Sep;49(9):1385-1391
pubmed: 28714975
Nature. 2012 Sep 6;489(7414):57-74
pubmed: 22955616
Nat Methods. 2015 Oct;12(10):963-965
pubmed: 26280331
Nature. 2012 Nov 8;491(7423):264-8
pubmed: 23064231
Science. 2017 Jun 23;356(6344):
pubmed: 28546318
Am J Hum Genet. 2015 Jul 2;97(1):139-52
pubmed: 26140449
Semin Immunopathol. 2015 Sep;37(5):443-51
pubmed: 26032405
Science. 2014 Sep 26;345(6204):1623-1627
pubmed: 25213377
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Science. 2014 Mar 7;343(6175):1246949
pubmed: 24604202
Nat Immunol. 2013 Oct;14(10):1054-63
pubmed: 23995234
Nat Genet. 2018 Mar;50(3):424-431
pubmed: 29379200
Science. 2015 Jul 24;349(6246):436-40
pubmed: 26206937
J Neuroimmunol. 2013 Sep 15;262(1-2):106-12
pubmed: 23845464
Genome Med. 2018 Feb 26;10(1):14
pubmed: 29482603
Nature. 2015 Feb 19;518(7539):337-43
pubmed: 25363779
Science. 2014 Sep 12;345(6202):1254665
pubmed: 25214635
Nat Genet. 2017 Oct;49(10):1511-1516
pubmed: 28892059
Nat Genet. 2019 Mar;51(3):404-413
pubmed: 30617256
J Exp Med. 2002 May 6;195(9):1129-43
pubmed: 11994418
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Nat Rev Rheumatol. 2010 Jan;6(1):40-9
pubmed: 20046205
Nature. 2011 Jun 15;474(7351):307-17
pubmed: 21677747
Nat Genet. 2018 Apr;50(4):621-629
pubmed: 29632380

Auteurs

Blagoje Soskic (B)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Open Targets, Wellcome Genome Campus, Cambridge, UK.

Eddie Cano-Gamez (E)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Open Targets, Wellcome Genome Campus, Cambridge, UK.

Deborah J Smyth (DJ)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Open Targets, Wellcome Genome Campus, Cambridge, UK.

Wendy C Rowan (WC)

Novel Human Genetics, GSK Research, GSK Medicines Research Centre, Stevenage, UK.

Nikolina Nakic (N)

Functional Genomics, Molecular Science and Technology R&D, GSK Medicines Research Centre, Stevenage, UK.

Jorge Esparza-Gordillo (J)

Human Genetics, GSK Research, GSK Medicines Research Centre, Stevenage, UK.

Lara Bossini-Castillo (L)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.

David F Tough (DF)

Epigenetics RU, Oncology R&D, GSK Medicines Research Centre, Stevenage, UK.

Christopher G C Larminie (CGC)

Human Genetics, GSK Research, GSK Medicines Research Centre, Stevenage, UK.

Paola G Bronson (PG)

Human Target Validation Core, RED Translational Biology, Biogen, Cambridge, MA, USA.

David Willé (D)

Biostatistics, GSK Research, GSK Medicines Research Centre, Stevenage, UK.

Gosia Trynka (G)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK. gosia@sanger.ac.uk.
Open Targets, Wellcome Genome Campus, Cambridge, UK. gosia@sanger.ac.uk.

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Classifications MeSH