Mendelian randomization analyses of genetically predicted circulating levels of cytokines with risk of Inflammatory bowel disease

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 12, 2023

Objective The literature has previously reported the associations between inflammatory bowel disease (IBD) and certain cytokines, such as CRP, IL-1, TNFα. To additionally evaluate causal relationships 41 cytokines IBD, a Mendelian randomization (MR) study was conducted. Methods two-sample MR investigation utilized data from three large publicly available genome-wide association studies (GWAS) on ulcerative colitis (UC), Crohn's (CD) genetic variants. Additionally, cytokine GWAS meta-analysis, including 8,293 healthy individuals, were incorporated into study. Causal exposures outcomes predominantly determined utilizing inverse variance-weighted methods. heterogeneity, pleiotropy, stability of these variants, MR-Egger intercept test, Cochran's Q leave-one-out sensitivity analysis Results findings revealed that IL13 linked to an elevated risk UC, CD, while MIF demonstrated correlation with CD. Conversely, TNF-related apoptosis-inducing ligand (TRAIL) decreased IBD UC. reverse analyses correlated levels Monokine Induced by Gamma Interferon (MIG) Stromal Cell-Derived Factor-1α (SDF1A), UC showed MIG IL10. CD stem cell factor (SCF) TNF-β. Conclusion In study, upstream regulatory factors five downstream identified for its subtypes, providing avenues developing new therapies IBD.

Language: Английский

Mendelian Randomization Analysis Reveals Metabolite and Inflammatory Factor Associations with Inflammatory Bowel Disease

Published: Jan. 1, 2023

This research, drawing from the UK Biobank and encompassing 115,078 participants, harnessed instrumental variables metabolomic quantitative trait loci studies to probe influence of plasma metabolites on Inflammatory Bowel Disease (IBD). High-throughput nuclear magnetic resonance (NMR) was employed non-fasting baseline EDTA samples measure metabolic biomarkers. The study utilized a specific GWAS dataset for IBD identified as ebi-a-GCST90038684, selected 41 inflammatory factors exposure variables. Using conventional genome-wide significance thresholds, SNPs related biomarkers were chosen, statistical tools like linkage disequilibrium (LD) clumping inverse variance weighted (IVW) method applied precise analyses. All evaluations performed R platform using various packages. Notably, Acetone, Glucose, Interleukin-2 receptor antagonist levels demonstrated significant causal relationship with IBD, an OR 1.001 95% CI 1.0004-1.002, p=0.002.

Language: Английский