Evaluation of causal associations between interleukin-18 levels and immune-mediated inflammatory diseases: a Mendelian randomization study.
Immune-mediated inflammatory diseases
Inflammatory bowel disease
Interleukin-18
Mendelian randomization
Systemic lupus erythematosus
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
29 Nov 2023
29 Nov 2023
Historique:
received:
28
06
2023
accepted:
19
11
2023
medline:
1
12
2023
pubmed:
30
11
2023
entrez:
29
11
2023
Statut:
epublish
Résumé
Altered interleukin (IL)-18 levels are associated with immune-mediated inflammatory diseases (IMIDs), but no studies have investigated their causal relationship. This study aimed to examine the causal associations between IL-18 and IMIDs. We performed a two-sample Mendelian randomization (MR) analysis. Genetic variants were selected from genome-wide association study datasets following stringent assessments. We then used these variants as instrumental variables to estimate the causal effects of IL-18 levels on the risk of developing five common IMIDs: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), and psoriasis. We used the inverse variance-weighted (IVW) method as the primary analysis, with sensitivity analyses performed to avoid potential bias. Reverse-direction MR analyses were performed to rule out the possibility of reverse associations. We found that genetically determined higher circulating IL-18 levels were causally associated with a higher risk for SLE (P We have demonstrated that elevated IL-18 levels increase the risk of SLE and IBD but not RA, AS, or psoriasis. The results enhanced our understanding of IL-18 in the pathology of IMIDs.
Sections du résumé
BACKGROUND
BACKGROUND
Altered interleukin (IL)-18 levels are associated with immune-mediated inflammatory diseases (IMIDs), but no studies have investigated their causal relationship. This study aimed to examine the causal associations between IL-18 and IMIDs.
METHODS
METHODS
We performed a two-sample Mendelian randomization (MR) analysis. Genetic variants were selected from genome-wide association study datasets following stringent assessments. We then used these variants as instrumental variables to estimate the causal effects of IL-18 levels on the risk of developing five common IMIDs: rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), and psoriasis. We used the inverse variance-weighted (IVW) method as the primary analysis, with sensitivity analyses performed to avoid potential bias. Reverse-direction MR analyses were performed to rule out the possibility of reverse associations.
RESULTS
RESULTS
We found that genetically determined higher circulating IL-18 levels were causally associated with a higher risk for SLE (P
CONCLUSIONS
CONCLUSIONS
We have demonstrated that elevated IL-18 levels increase the risk of SLE and IBD but not RA, AS, or psoriasis. The results enhanced our understanding of IL-18 in the pathology of IMIDs.
Identifiants
pubmed: 38031150
doi: 10.1186/s12920-023-01744-z
pii: 10.1186/s12920-023-01744-z
pmc: PMC10685486
doi:
Substances chimiques
Immunomodulating Agents
0
Interleukin-18
0
IL18 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
306Subventions
Organisme : the Scientific research project of Guangdong Provincial Bureau of Traditional Chinese Medicine
ID : 20231059
Organisme : the National Natural Science Foundation of China
ID : 82302044
Organisme : the Guangdong Clinical Research Center of Immune Disease
ID : 2020B1111170008
Organisme : the Science and Technology Planning Project of Guangdong Province, China
ID : 2020B1515130005
Informations de copyright
© 2023. The Author(s).
Références
J Nephropathol. 2016 Jan;5(1):28-33
pubmed: 27047807
BMJ. 2018 Jul 12;362:k601
pubmed: 30002074
Int J Mol Sci. 2016 Aug 03;17(8):
pubmed: 27527149
Lupus. 2022 Feb;31(2):187-193
pubmed: 35042378
J Biomed Biotechnol. 2011;2011:271694
pubmed: 21403825
J Autoimmun. 2010 Mar;34(2):121-6
pubmed: 19699611
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14181-6
pubmed: 14615579
Cytokine. 2022 Feb;150:155781
pubmed: 34923222
Ann N Y Acad Sci. 2009 Sep;1173:301-9
pubmed: 19758166
Genet Epidemiol. 2013 Nov;37(7):658-65
pubmed: 24114802
Nat Commun. 2021 Feb 19;12(1):1146
pubmed: 33608531
Genet Epidemiol. 2016 May;40(4):304-14
pubmed: 27061298
Am J Clin Nutr. 2006 Feb;83(2):447S-455S
pubmed: 16470011
Nat Immunol. 2023 Sep;24(9):1540-1551
pubmed: 37563310
Am J Epidemiol. 2013 Oct 1;178(7):1177-84
pubmed: 23863760
J Leukoc Biol. 2003 Feb;73(2):213-24
pubmed: 12554798
J Immunol. 2001 Jan 1;166(1):517-21
pubmed: 11123331
Eur Cytokine Netw. 2010 Dec;21(4):264-71
pubmed: 21126942
J Clin Invest. 2001 Dec;108(12):1825-32
pubmed: 11748266
Postgrad Med J. 2007 Apr;83(978):251-60
pubmed: 17403952
BMJ. 2021 Oct 26;375:n2233
pubmed: 34702754
J Immunol. 2001 Jun 15;166(12):7014-8
pubmed: 11390444
Arch Dermatol Res. 2017 May;309(4):315-321
pubmed: 28299442
PLoS One. 2015 Oct 14;10(10):e0140173
pubmed: 26465326
Elife. 2018 May 30;7:
pubmed: 29846171
Swiss Med Wkly. 2009 Mar 7;139(9-10):140-5
pubmed: 19274491
Nat Rev Rheumatol. 2015 Oct;11(10):616-20
pubmed: 26122951
N Engl J Med. 2021 Aug 12;385(7):628-639
pubmed: 34379924
Acta Derm Venereol. 2003;83(4):262-5
pubmed: 12926796
Gut. 2002 Jun;50(6):812-20
pubmed: 12010883
JAMA. 2021 Oct 26;326(16):1614-1621
pubmed: 34698778
Front Immunol. 2019 May 14;10:1091
pubmed: 31139196
Rheumatology (Oxford). 2016 Dec;55(12):2237-2247
pubmed: 27616144
Eur J Drug Metab Pharmacokinet. 2006 Apr-Jun;31(2):109-16
pubmed: 16898079
Genet Epidemiol. 2016 Nov;40(7):597-608
pubmed: 27625185
Int J Epidemiol. 2015 Apr;44(2):512-25
pubmed: 26050253
Arch Dermatol Res. 2001 Jul;293(7):334-42
pubmed: 11550806
Nat Genet. 2018 May;50(5):693-698
pubmed: 29686387
Nature. 2023 Jan;613(7944):508-518
pubmed: 36653562
J Immunol. 2001 Nov 1;167(9):5338-47
pubmed: 11673550
Eur Cytokine Netw. 2005 Jan-Mar;16(1):27-33
pubmed: 15809203
Sci Rep. 2019 Jun 28;9(1):9386
pubmed: 31253830
Nat Rev Immunol. 2021 Oct;21(10):680-686
pubmed: 34518662
Eur Cytokine Netw. 2006 Dec;17(4):224-52
pubmed: 17353157
Front Immunol. 2018 Jun 07;9:1250
pubmed: 29930551
Nat Genet. 2015 Dec;47(12):1457-1464
pubmed: 26502338
Arch Med Sci. 2011 Aug;7(4):713-9
pubmed: 22291810
Clin Rheumatol. 2004 Jun;23(3):225-9
pubmed: 15168150
Front Immunol. 2013 Oct 08;4:289
pubmed: 24115947
Clin Exp Med. 2009 Sep;9(3):215-21
pubmed: 19225717
J Immunother. 2002 Mar-Apr;25 Suppl 1:S65-7
pubmed: 12048353
J Immunol. 1997 Mar 15;158(6):3009-16
pubmed: 9058840
Clin Rheumatol. 2006 Jul;25(4):448-52
pubmed: 16362448
Nat Commun. 2017 May 24;8:15382
pubmed: 28537254
Am J Gastroenterol. 2002 Nov;97(11):2820-8
pubmed: 12425554
Nat Rev Methods Primers. 2022 Feb 10;2:
pubmed: 37325194
J Clin Invest. 1999 Nov;104(10):1393-401
pubmed: 10562301
Stat Med. 2015 Sep 20;34(21):2926-40
pubmed: 25950993
Int Arch Allergy Immunol. 2020;181(10):799-806
pubmed: 32781445
J Immunol. 2000 Dec 1;165(11):6553-8
pubmed: 11086098
Ann Rheum Dis. 2002 Aug;61(8):726-9
pubmed: 12117681
Rheumatol Int. 2009 Dec;30(2):187-91
pubmed: 19387647
J Immunol. 1999 Jun 1;162(11):6829-35
pubmed: 10352304
Nat Genet. 2022 Nov;54(11):1640-1651
pubmed: 36333501