Dataset Information

Association between Inflammatory Bowel Disease and Iridocyclitis: A Mendelian Randomization Study.

ABSTRACT:

Background

Iridocyclitis (IC) is a common extraintestinal manifestation of inflammatory bowel disease (IBD). Observational studies showed patients with ulcerative colitis (UC) and Crohn's disease (CD) both have a higher risk of IC. However, due to the inherent limitations of observational studies, the association and its directionality between the two forms of IBD and IC remain undiscerned.

Methods

Genetic variants for IBD and IC were selected as instruments from genome-wide association studies (GWAS) and FinnGen database as instrumental variables, respectively. A bidirectional Mendelian randomization (MR) and multivariable MR were performed successively. Three different MR methods were performed to determine the causal association, including inverse-variance weighted (IVW), MR Egger, and weighted median, whereas IVW was used as the main analysis. Different methods for sensitivity analysis were used, including MR-Egger intercept test, MR Pleiotropy RESidual Sum and Outlier test, Cochran's Q test, and leave-one-out analysis.

Results

Bidirectional MR suggested both UC and CD were positively associated with IC as a whole, acute and subacute IC, and chronic IC. However, in the MVMR analysis, only the association from CD to IC remained stable. In the reverse analysis, no association was observed from IC to UC or CD.

Conclusions

Both UC and CD are associated with an increased risk of IC compared with healthy individuals. However, the association between CD and IC is stronger. In the reverse direction, patients with IC do not suffer a higher risk of UC or CD. We emphasize the importance of ophthalmic examinations for IBD patients, especially for CD patients.

SUBMITTER: Meng Y

PROVIDER: S-EPMC9960523 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Association between Inflammatory Bowel Disease and Iridocyclitis: A Mendelian Randomization Study.

Meng Yang Y Tan Zongbiao Z Liu Chuan C Dong Weiguo W Chen Changzheng C

Journal of clinical medicine 20230206 4

<h4>Background</h4>Iridocyclitis (IC) is a common extraintestinal manifestation of inflammatory bowel disease (IBD). Observational studies showed patients with ulcerative colitis (UC) and Crohn's disease (CD) both have a higher risk of IC. However, due to the inherent limitations of observational studies, the association and its directionality between the two forms of IBD and IC remain undiscerned.<h4>Methods</h4>Genetic variants for IBD and IC were selected as instruments from genome-wide assoc ...[more]

PMID: 36835817

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Project description:BackgroundAn association has been identified between inflammatory bowel disease (IBD) and frailty; however, the causal nature of this connection remains uncertain. We consequently conducted a two-sample Mendelian randomization (MR) analysis to explore this particular association.MethodsWe acquired distinct datasets for inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), and frailty from the published genome-wide association studies (GWAS) database, meticulously selecting instrumental variables (IVs). Subsequently, we employed a bidirection MR to examine the causal relationship between IBD (including CD and UC) and frailty. We utilized statistical methods, with a primary emphasis on inverse-variance weighted (IVW), accompanied by a series of sensitivity analyses to confirm heterogeneity and pleiotropy influenced the outcomes of the MR.ResultsWe found positive causal effects of genetically increased frailty risk on IBD (OR: 1.015, 95% CI 1.005-1.025, P = 0.004). Furthermore, when scrutinizing specific IBD subtypes, both Crohn's disease (CD) and ulcerative colitis (UC) demonstrated an increased predisposition to frailty (OR: 1.018, 95% CI 1.01-1.027, P < 0.05) and (OR = 1.016, 95% CI 1.005-1.027, P < 0.05). Nevertheless, despite the consistent trends observed in the weighted median and MR-Egger regression analyses for both conditions, statistical significance remained elusive. Notably, the results of the inverse MR analysis did not establish an association between frailty and an elevated risk of IBD development.ConclusionsOur research indicates that IBD, encompassing both CD and UC, may augment the propensity for frailty. Clinical practitioners must prioritize early frailty assessment in individuals afflicted with inflammatory bowel disease, inclusive of Crohn's disease and ulcerative colitis, facilitating proactive measures and timely interventions. However, our findings do not provide evidence supporting a causal effect of frailty on IBD (including CD and UC). Consequently, further studies are essential to explore the intricate mechanisms that clarify the effect of frailty on IBD.

Project description:Background: An association between inflammatory bowel disease (IBD) [which includes ulcerative colitis (UC) and Crohn's disease (CD)] and IgA nephropathy (IgAN) has been discovered in observational studies, but the causal relationship is still unknown. The aim of this study was to clarify the causal link between IBD (which includes UC and CD) and IgAN via a two-sample Mendelian randomization (MR) analysis. Methods: Eligible single-nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) for analyses and were obtained from the publicly available genome-wide association study (GWAS) summary statistics. Inverse-variance weighting (IVW), Mendelian randomization-Egger (MR-Egger) regression, the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test, and the weighted median were utilized to obtain the results. The MR-PRESSO test and MR-Egger regression were also performed to detect and correct horizontal pleiotropy. The Cochran's Q test and "leave-one-out" analysis were also conducted to assess the stability and reliability of the MR results. Results: This study found that IBD, UC, and CD all had significant positive causal effects on IgAN risk (IBD: OR = 1.58, 95% CI 1.15-2.16, p = 4.53 × 10-3; UC: OR = 1.55, 95% CI 1.14-2.11, p = 4.88 × 10-3; CD: OR = 1.57, 95% CI 1.21-2.03, p = 5.97 × 10-4). No significant horizontal pleiotropic effect was found for the causal association between IBD, UC, CD, and the risk of IgAN. Cochran's Q test identified no evidence of heterogeneity for the IV estimates. The "leave-one-out" sensitivity analysis also revealed that the MR results were robust. Conclusion: The results of this two-sample MR analysis supported that IBD, UC, and CD were causally associated with the risk of IgAN, while there was no sufficient evidence for the causal effect of IgAN on IBD, UC, or CD. Our findings provide theoretical support and a new perspective for the diagnosis and treatment of these two diseases.

Dataset Information

Association between Inflammatory Bowel Disease and Iridocyclitis: A Mendelian Randomization Study.

Background

Methods

Results

Conclusions

Publications

Association between Inflammatory Bowel Disease and Iridocyclitis: A Mendelian Randomization Study.

Similar Datasets

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