Association analysis of juvenile idiopathic arthritis genetic susceptibility factors in Estonian patients.
Genome-wide association study
Juvenile idiopathic arthritis
Rheumatoid arthritis
Journal
Clinical rheumatology
ISSN: 1434-9949
Titre abrégé: Clin Rheumatol
Pays: Germany
ID NLM: 8211469
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
received:
17
01
2021
accepted:
27
04
2021
revised:
26
04
2021
pubmed:
9
6
2021
medline:
29
9
2021
entrez:
8
6
2021
Statut:
ppublish
Résumé
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Genetic association studies have revealed several JIA susceptibility loci with the strongest effect size observed in the human leukocyte antigen (HLA) region. Genome-wide association studies have augmented the number of JIA-associated loci, particularly for non-HLA genes. The aim of this study was to identify new associations at non-HLA loci predisposing to the risk of JIA development in Estonian patients. We performed genome-wide association analyses in an entire JIA case-control sample (All-JIA) and in a case-control sample for oligoarticular JIA, the most prevalent JIA subtype. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. After imputation, 16,583,468 variants were analyzed in 263 cases and 6956 controls. We demonstrated nominal evidence of association for 12 novel non-HLA loci not previously implicated in JIA predisposition. We replicated known JIA associations in CLEC16A and VCTN1 regions in the oligoarticular JIA sample. The strongest associations in the All-JIA analysis were identified at PRKG1 (P = 2,54 × 10 This study increases the number of known JIA risk loci and provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that confer susceptibility to JIA in Estonian patients. Key Points • Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease with heterogeneous presentation and genetic predisposition. • Present genome-wide association study for Estonian JIA patients is first of its kind in Northern and Northeastern Europe. • The results of the present study increase the knowledge about JIA risk loci replicating some previously described associations, so adding weight to their relevance and describing novel loci. • The study provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis.
Sections du résumé
BACKGROUND
BACKGROUND
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Genetic association studies have revealed several JIA susceptibility loci with the strongest effect size observed in the human leukocyte antigen (HLA) region. Genome-wide association studies have augmented the number of JIA-associated loci, particularly for non-HLA genes. The aim of this study was to identify new associations at non-HLA loci predisposing to the risk of JIA development in Estonian patients.
METHODS
METHODS
We performed genome-wide association analyses in an entire JIA case-control sample (All-JIA) and in a case-control sample for oligoarticular JIA, the most prevalent JIA subtype. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. After imputation, 16,583,468 variants were analyzed in 263 cases and 6956 controls.
RESULTS
RESULTS
We demonstrated nominal evidence of association for 12 novel non-HLA loci not previously implicated in JIA predisposition. We replicated known JIA associations in CLEC16A and VCTN1 regions in the oligoarticular JIA sample. The strongest associations in the All-JIA analysis were identified at PRKG1 (P = 2,54 × 10
CONCLUSION
CONCLUSIONS
This study increases the number of known JIA risk loci and provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that confer susceptibility to JIA in Estonian patients. Key Points • Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease with heterogeneous presentation and genetic predisposition. • Present genome-wide association study for Estonian JIA patients is first of its kind in Northern and Northeastern Europe. • The results of the present study increase the knowledge about JIA risk loci replicating some previously described associations, so adding weight to their relevance and describing novel loci. • The study provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis.
Identifiants
pubmed: 34101054
doi: 10.1007/s10067-021-05756-x
pii: 10.1007/s10067-021-05756-x
pmc: PMC8463396
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4157-4165Subventions
Organisme : Estonian Science Foundation
ID : ETF9255
Informations de copyright
© 2021. The Author(s).
Références
Genes Immun. 2015 Jan-Feb;16(1):15-23
pubmed: 25338677
Arthritis Rheumatol. 2017 Nov;69(11):2222-2232
pubmed: 28719732
Mediators Inflamm. 2017;2017:7623145
pubmed: 28255205
Mol Immunol. 2015 Oct;67(2 Pt B):532-9
pubmed: 26265114
PLoS One. 2017 Feb 9;12(2):e0171961
pubmed: 28182665
Ann Rheum Dis. 2010 Apr;69(4):666-70
pubmed: 19470526
Genes Immun. 2007 Sep;8(6):480-91
pubmed: 17568789
Joint Bone Spine. 2014 Mar;81(2):112-7
pubmed: 24210707
Inflamm Res. 2014 Jun;63(6):441-50
pubmed: 24496593
Immunity. 2016 Jan 19;44(1):131-142
pubmed: 26750311
J Rheumatol. 2004 Feb;31(2):390-2
pubmed: 14760812
Ann Rheum Dis. 2014 Jun;73(6):1198-201
pubmed: 24347572
Ann Rheum Dis. 2017 Jun;76(6):1150-1158
pubmed: 28314753
Arthritis Res Ther. 2014 Aug 20;16(4):414
pubmed: 25138370
Arthritis Rheum. 2012 Jul;64(7):2191-200
pubmed: 22275266
Genes Immun. 2017 Jan;18(1):48-56
pubmed: 28053322
Nat Genet. 2009 Dec;41(12):1313-8
pubmed: 19898481
Sci Transl Med. 2009 Dec 9;1(10):10ra21
pubmed: 20368159
Clin Rheumatol. 2018 Feb;37(2):289-296
pubmed: 29302826
Nat Genet. 2009 Nov;41(11):1228-33
pubmed: 19838195
Mol Cell Biochem. 2019 Sep;459(1-2):141-150
pubmed: 31297660
Int J Biol Sci. 2017 Feb 25;13(3):358-366
pubmed: 28367100
PLoS One. 2015 Apr 22;10(4):e0124254
pubmed: 25901943
Nature. 2014 Feb 20;506(7488):376-81
pubmed: 24390342
J Immunol. 2011 May 1;186(9):5085-94
pubmed: 21430220
Ann Rheum Dis. 2010 Aug;69(8):1471-4
pubmed: 19734133
Ann Rheum Dis. 2012 Jul;71(7):1117-21
pubmed: 22294642
Nat Genet. 2013 Jun;45(6):664-9
pubmed: 23603761
Rheumatology (Oxford). 2015 Apr;54(4):712-21
pubmed: 25261692
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19849-54
pubmed: 18056638
Pharm Biol. 2020 Dec;58(1):146-151
pubmed: 31971852
Mol Med Rep. 2016 Aug;14(2):1587-93
pubmed: 27356888
Ann Rheum Dis. 2019 Jan;78(1):36-42
pubmed: 30297333
Arthritis Rheumatol. 2014 May;66(5):1352-62
pubmed: 24782191
Clin Exp Rheumatol. 2007 Jul-Aug;25(4):649-53
pubmed: 17888227
Arthritis Rheum. 2009 Jan;60(1):258-63
pubmed: 19116933
J Autoimmun. 2018 Feb;87:69-81
pubmed: 29254845
Ann Rheum Dis. 2015 Dec;74(12):2193-8
pubmed: 25057181
J Cell Biochem. 2017 Jun;118(6):1308-1315
pubmed: 27505147
Clin Rheumatol. 2016 Apr;35(4):961-71
pubmed: 26474773
J Biol Chem. 2010 Aug 6;285(32):24639-45
pubmed: 20522558
J Biol Chem. 2015 Dec 25;290(52):30910-23
pubmed: 26518873
Front Pharmacol. 2019 Apr 10;10:367
pubmed: 31024321
Ann Rheum Dis. 2010 Jan;69(1):309-11
pubmed: 19221398
Nat Genet. 2010 Dec;42(12):1118-25
pubmed: 21102463
Nat Immunol. 2019 Feb;20(2):141-151
pubmed: 30643265
Arthritis Res Ther. 2019 Jan 29;21(1):39
pubmed: 30696478
Cell. 2015 Apr 9;161(2):387-403
pubmed: 25772697
Arthritis Rheumatol. 2016 Jul;68(7):1603-13
pubmed: 26895230
J Immunol. 2006 Aug 15;177(4):2681-90
pubmed: 16888030