Association between inflammatory bowel disease and interleukins, chemokines: a two-sample bidirectional mendelian randomization study

Abstract

BackgroundMendelian randomization (MR) was used to evaluate the bidirectional causal relationship between inflammatory bowel disease (IBD) and interleukins (ILs), chemokines.MethodsGenetic instruments and summary data of five ILs and six chemokines were obtained from a genome-wide association study database, and instrumental variables related to IBD were obtained from the FinnGen Consortium. Inverse variance weighting (IVW) was used as the main MR analysis method, and several other MR methods including MR-Egger and weighted median were used to confirm the reliability of the results. Sensitivity analyses such as heterogeneity and pleiotropy were also performed.ResultsThe IVW method provided evidence to support that genetically predicted IL-16, IL-18, and CXCL10 significantly positively correlated with IBD, while IL-12p70 and CCL23 significantly negatively correlated with IBD. IL-16 and IL-18 had a suggestive association with an increased risk of ulcerative colitis (UC), and CXCL10 had a suggestive association with an increased risk of Crohn’s disease (CD). However, there was no evidence to support that IBD and two main subtypes (UC and CD) are associated with changes in the levels of ILs and chemokines. The results of the sensitivity analyses were robust and no evidence of heterogeneity and horizontal pleiotropy was observed.ConclusionsThe present study showed that some ILs and chemokines affect IBD, but IBD and its main subtypes (UC and CD) have no effect on the level changes of ILs and chemokines.

Associations of inflammatory cytokines with inflammatory bowel disease: a Mendelian randomization study

“…The findings indicated significant positive correlations of IL-16, IL-18, and CXCL10 with IBD, contrasting with IL-12p70 and CCL23, which showed significant negative correlations. Additionally, IL-16 and IL-18 suggested an increased risk of UC, while CXCL10 hinted at an increased risk of CD ( 20 ).…”

Mendelian randomisation analysis for intestinal disease: achievement and future

“…57 Total cholesterol, triglycerides and low-density lipoprotein seem to be protective factors for UC in MR studies. 13 58 INFLAMMATORY PROTEIN BIOMARKERS Genetically predicted interleukin (IL)-16, 59 IL-18 59 and CXCL10 59 were related to an increased risk of inflammatory bowel disease significantly, whereas IL-12p70 59 and Open access CCL23 59 were inversely associated with the inflammatory bowel disease. 59 A bidirectional MR investigation revealed that CXCL9, CCL11 and CASP8 were associated with an increased risk of UC; furthermore, it was observed that genetic predisposition to UC did not exert any influence on these three inflammation protein levels.…”

“…13 58 INFLAMMATORY PROTEIN BIOMARKERS Genetically predicted interleukin (IL)-16, 59 IL-18 59 and CXCL10 59 were related to an increased risk of inflammatory bowel disease significantly, whereas IL-12p70 59 and Open access CCL23 59 were inversely associated with the inflammatory bowel disease. 59 A bidirectional MR investigation revealed that CXCL9, CCL11 and CASP8 were associated with an increased risk of UC; furthermore, it was observed that genetic predisposition to UC did not exert any influence on these three inflammation protein levels. 60 Genetically predicted C reactive protein level was inversely associated with the increased risk of inflammatory bowel disease in an MR study, while the association was not significant after excluding SNPs with heterogeneity.…”

Causal relationship between circulating immune cells and inflammatory bowel disease: A Mendelian randomization analysis

“…[ 7 ] The use of MR analysis has increased in recent years for identifying potential IBD risk factors. [ 8 – 11 ] A number of MR studies have also provided evidence linking inflammatory biomarkers to IBD, such as interleukin (IL)-17, [ 12 ] IL-18, [ 13 , 14 ] C-X–C motif chemokine 9, [ 15 ] and C–C motif chemokine 23. [ 13 ] Despite this, the relationship between circulating immune cells and the risk of IBD has not been thoroughly examined.…”

“…[ 8 – 11 ] A number of MR studies have also provided evidence linking inflammatory biomarkers to IBD, such as interleukin (IL)-17, [ 12 ] IL-18, [ 13 , 14 ] C-X–C motif chemokine 9, [ 15 ] and C–C motif chemokine 23. [ 13 ] Despite this, the relationship between circulating immune cells and the risk of IBD has not been thoroughly examined. Thus, we conducted a bidirectional 2-sample MR analysis using genome-wide association study (GWAS) data to determine the causal relationship between immune cell traits and IBD.…”