Translational Analysis of Moderate to Severe Asthma GWAS Signals Into Candidate Causal Genes and Their Functional, Tissue-Dependent and Disease-Related Associations.
GWAS
SNP
causal genes
eQTL
moderate to severe asthma
Journal
Frontiers in allergy
ISSN: 2673-6101
Titre abrégé: Front Allergy
Pays: Switzerland
ID NLM: 9918227355906676
Informations de publication
Date de publication:
2021
2021
Historique:
received:
09
07
2021
accepted:
06
09
2021
entrez:
7
4
2022
pubmed:
8
4
2022
medline:
8
4
2022
Statut:
epublish
Résumé
Asthma affects more than 300 million people globally and is both under diagnosed and under treated. The most recent and largest genome-wide association study investigating moderate to severe asthma to date was carried out in 2019 and identified 25 independent signals. However, as new and in-depth downstream databases become available, the translational analysis of these signals into target genes and pathways is timely. In this study, unique (U-BIOPRED) and publicly available datasets (HaploReg, Open Target Genetics and GTEx) were investigated for the 25 GWAS signals to identify 37 candidate causal genes. Additional traits associated with these signals were identified through PheWAS using the UK Biobank resource, with asthma and eosinophilic traits amongst the strongest associated. Gene expression omnibus dataset examination identified 13 candidate genes with altered expression profiles in the airways and blood of asthmatic subjects, including
Identifiants
pubmed: 35386986
doi: 10.3389/falgy.2021.738741
pmc: PMC8974692
doi:
Types de publication
Journal Article
Langues
eng
Pagination
738741Informations de copyright
Copyright © 2021 Portelli, Rakkar, Hu, Guo, Adcock and Sayers.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Nat Methods. 2013 Dec;10(12):1209-10
pubmed: 24122041
JCI Insight. 2020 Apr 23;5(8):
pubmed: 32324168
Nucleic Acids Res. 2009 Jan;37(1):1-13
pubmed: 19033363
Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16648-53
pubmed: 23011799
J Allergy Clin Immunol. 2012 Oct;130(4):861-8.e7
pubmed: 22694930
Nat Genet. 2018 Nov;50(11):1593-1599
pubmed: 30349118
Mutat Res. 2010 Aug 7;690(1-2):24-39
pubmed: 19769993
PLoS Genet. 2019 Dec 12;15(12):e1008489
pubmed: 31830040
Adv Immunol. 2017;135:1-52
pubmed: 28826527
Allergy Asthma Immunol Res. 2019 Mar;11(2):170-187
pubmed: 30661310
J Asthma. 2016 Oct;53(8):775-82
pubmed: 27050946
Allergy. 2015 Oct;70(10):1309-18
pubmed: 26119467
Am J Respir Crit Care Med. 2016 Nov 15;194(10):1296-1299
pubmed: 27845589
Eur J Hum Genet. 2008 Sep;16(9):1083-90
pubmed: 18382474
Nucleic Acids Res. 2002 Jan 1;30(1):207-10
pubmed: 11752295
J Allergy Clin Immunol. 2019 Dec;144(6):1648-1659.e9
pubmed: 31330218
Mediators Inflamm. 2019 Dec 30;2019:2609737
pubmed: 32082072
BMJ Open Respir Res. 2020 Apr;7(1):
pubmed: 32273395
Expert Opin Investig Drugs. 2019 Nov;28(11):931-940
pubmed: 31549891
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
J Allergy Clin Immunol. 2005 Sep;116(3):477-86; quiz 487
pubmed: 16159612
Respirology. 2011 Apr;16(3):396-406
pubmed: 21276132
Allergy. 2020 Aug;75(8):1902-1917
pubmed: 32460363
Nat Commun. 2016 Sep 01;7:12596
pubmed: 27581382
J Invest Dermatol. 2012 Mar;132(3 Pt 2):751-62
pubmed: 22158554
Respir Res. 2011 Jun 23;12:86
pubmed: 21699702
Mediators Inflamm. 2015;2015:879783
pubmed: 25878402
Nucleic Acids Res. 2012 Jan;40(Database issue):D930-4
pubmed: 22064851
Am J Transl Res. 2020 Apr 15;12(4):1168-1183
pubmed: 32355534
Hum Genet. 2014 Jul;133(7):815-45
pubmed: 24496500
Clin Exp Allergy. 2018 Feb;48(2):147-155
pubmed: 29266469
Nat Genet. 2011 Jul 31;43(9):887-92
pubmed: 21804549
Lancet. 2000 Dec 23-30;356(9248):2144-8
pubmed: 11191542
N Engl J Med. 2010 Sep 23;363(13):1211-1221
pubmed: 20860503
Lancet Respir Med. 2020 Oct;8(10):1045-1056
pubmed: 32910899
Lancet. 2017 Sep 16;390(10100):1211-1259
pubmed: 28919117
Annu Rev Immunol. 2009;27:591-619
pubmed: 19132916
BMC Pulm Med. 2020 Jun 29;20(1):184
pubmed: 32600318
Nat Genet. 2018 Jan;50(1):42-53
pubmed: 29273806
Clin Transl Immunology. 2017 Dec 15;6(12):e165
pubmed: 29333270
PLoS One. 2013;8(4):e60111
pubmed: 23565190
Lancet Respir Med. 2019 Jan;7(1):20-34
pubmed: 30552067
Allergy Asthma Clin Immunol. 2013 Feb 01;9(1):4
pubmed: 23369242
J Allergy Clin Immunol. 2012 Aug;130(2):516-22.e4
pubmed: 22541248
Hum Immunol. 2014 Aug;75(8):930-9
pubmed: 24994462
PLoS One. 2013 Jul 02;8(7):e67560
pubmed: 23844029
Am J Respir Crit Care Med. 2016 Jan 1;193(1):98-100
pubmed: 26720789
Thorax. 2021 Feb 25;:
pubmed: 33632765
Nucleic Acids Res. 2010 Jul;38(Web Server issue):W214-20
pubmed: 20576703
J Physiol. 2017 Jun 15;595(12):4109-4115
pubmed: 28229460
G3 (Bethesda). 2017 Aug 7;7(8):2855-2858
pubmed: 28663344
BMC Pulm Med. 2020 Oct 16;20(1):270
pubmed: 33066754
Mucosal Immunol. 2014 Sep;7(5):1175-85
pubmed: 24518246
Nucleic Acids Res. 2019 Jan 8;47(D1):D1056-D1065
pubmed: 30462303
Clin Exp Allergy. 1998 May;28(5):568-77
pubmed: 9645593
Acta Med Iran. 2017 May;55(5):352-353
pubmed: 28724278
Immunol Rev. 2017 Jul;278(1):63-86
pubmed: 28658551
J Biol Chem. 2013 Feb 22;288(8):5616-23
pubmed: 23319592
J Allergy Clin Immunol. 2015 Apr;135(4):896-902
pubmed: 25441637
Front Immunol. 2018 Feb 06;9:175
pubmed: 29472925
Lancet Respir Med. 2014 Mar;2(3):226-37
pubmed: 24621684
Nat Genet. 2009 Feb;41(2):216-20
pubmed: 19122664
Nat Immunol. 2015 Jan;16(1):45-56
pubmed: 25521684
J Clin Med. 2019 Sep 02;8(9):
pubmed: 31480806
Am J Hum Genet. 2019 Apr 4;104(4):665-684
pubmed: 30929738
Am J Respir Crit Care Med. 2018 Jan 1;197(1):22-37
pubmed: 28910134
J Allergy Clin Immunol. 2018 Sep;142(3):749-764.e3
pubmed: 29307657
J Allergy Clin Immunol. 1999 Jan;103(1 Pt 1):11-24
pubmed: 9893178
Am J Respir Cell Mol Biol. 2007 Sep;37(3):273-90
pubmed: 17463395
Science. 2012 Sep 7;337(6099):1190-5
pubmed: 22955828
Am J Respir Crit Care Med. 2003 Mar 1;167(5):751-7
pubmed: 12468439
PLoS Med. 2015 Mar 31;12(3):e1001779
pubmed: 25826379
Nucleic Acids Res. 2021 Jan 8;49(D1):D480-D489
pubmed: 33237286
Cell Tissue Res. 2017 Mar;367(3):551-569
pubmed: 28190087
Nat Commun. 2018 Oct 16;9(1):4285
pubmed: 30327483
Annu Rev Immunol. 2001;19:423-74
pubmed: 11244043
Nat Rev Dis Primers. 2015 Sep 10;1:15025
pubmed: 27189668
Bioinformatics. 2015 Nov 1;31(21):3555-7
pubmed: 26139635
Nat Immunol. 2000 Aug;1(2):132-7
pubmed: 11248805
Diabetes Care. 2015 Jan;38(1):113-8
pubmed: 25368105
Am J Physiol Lung Cell Mol Physiol. 2003 Sep;285(3):L730-9
pubmed: 12794003
Clin Exp Allergy. 2015 Jan;45(1):21-31
pubmed: 24766371
JCI Insight. 2016 Sep 8;1(14):e87871
pubmed: 27699235
Am J Respir Crit Care Med. 2017 May 15;195(10):1311-1320
pubmed: 27925796
G3 (Bethesda). 2020 Nov 5;10(11):4049-4062
pubmed: 32900903
Can Respir J. 2010 Jul-Aug;17(4):e85-93
pubmed: 20808979