Association Between Inflammatory Bowel Disease and Atopic Dermatitis: A Two-Sample Mendelian Randomization Study

2021 ◽  
Author(s):  
Xiaoyu Gu ◽  
Xinchen Ke ◽  
Minxue Shen ◽  
Mi Zhang ◽  
Juan Su
Keyword(s):  
Inflammatory Bowel Disease ◽  
Atopic Dermatitis ◽  
Bowel Disease ◽  
Mendelian Randomization ◽  
Inflammatory Bowel

Causal Association Between Atopic Dermatitis and Inflammatory Bowel Disease: A 2-Sample Bidirectional Mendelian Randomization Study

2021 ◽  
Author(s):  
Christa Meisinger ◽  
Dennis Freuer
Keyword(s):  
Inflammatory Bowel Disease ◽  
Atopic Dermatitis ◽  
Bowel Disease ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
The Other ◽  
Uk Biobank ◽  
Inflammatory Bowel ◽  
The Uk

Abstract Background Observational studies postulated an association between atopic dermatitis (AD) and inflammatory bowel disease (IBD). However, it remains unclear whether this relationship is causal. Methods To determine whether AD is causally related to IBD and vice versa, a 2-sample Mendelian randomization study was conducted. Independent genetic instruments from the largest available genome-wide association study for AD (EAGLE eczema consortium without the 23andMe study including 10,788 cases and 30,047 controls) were used to investigate the association with IBD in the UK Biobank study (7045 cases, 456,327 controls) and a second European IBD sample (12,882 cases, 21,770 controls). Results Atopic dermatitis was strongly associated with higher risk of IBD as a whole (odds ratio [OR], 1.107; 95% confidence interval [CI], 1.035; 1.183; P = .003) in the UK Biobank study. The positive association was not significant in the other IBD study (OR, 1.114; 95% CI, 0.956; 1.298), but in meta-analyses of results from the 2 studies, the strong association could be confirmed (OR, 1.11; 95% CI, 1.04; 1.18). When evaluating the causal relationship in the other direction, IBD as a whole did not show an association with AD. Subtype analyses revealed that AD was suggestively associated with ulcerative colitis (UC; OR, 1.149; 95% CI, 1.018; 1.297) but not Crohn’s disease (CD). However, there was a suggestive association between CD and AD (OR, 1.034; 95% CI, 1.004; 1.064) but not UC and AD. Conclusions This study supports a causal effect between AD and IBD—but not between IBD and AD. There seems to be considerable differences between UC and CD regarding their specific associations with AD. These findings have implications for the management of IBD and AD in clinical practice.

New-onset inflammatory bowel disease in adults with atopic dermatitis

2017 ◽  
Vol 31 (8) ◽  
pp. e363-e365 ◽  
Author(s):  
A. Egeberg ◽  
N. Wienholtz ◽  
G.H. Gislason ◽  
L. Skov ◽  
J.P. Thyssen
Keyword(s):  
Inflammatory Bowel Disease ◽  
Atopic Dermatitis ◽  
Bowel Disease ◽  
Inflammatory Bowel ◽  
New Onset

scholarly journals Assessment of Causal Direction Between Gut Microbiota and Inflammatory Bowel Disease: A Mendelian Randomization Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zi-Jia Zhang ◽  
Hong-Lei Qu ◽  
Na Zhao ◽  
Jing Wang ◽  
Xiu-Yan Wang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Bowel Disease ◽  
Pathogenic Bacteria ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Intestinal Bacteria ◽  
Social Program ◽  
Significance Level ◽  
Inflammatory Bowel

BackgroundRecent studies have shown that the gut microbiota is closely related to the pathogenesis of Inflammatory Bowel Disease (IBD), but the causal nature is largely unknown. The purpose of this study was to assess the causal relationship between intestinal bacteria and IBD and to identify specific pathogenic bacterial taxa via the Mendelian randomization (MR) analysis.Materials and MethodsMR analysis was performed on genome-wide association study (GWAS) summary statistics of gut microbiota and IBD. Specifically, the TwinsUK microbiota GWAS (N = 1,126 twin pairs) was used as exposure. The UK inflammatory bowel disease (UKIBD) and the Understanding Social Program (USP) study GWAS (N = 48,328) was used as discovery outcome, and the British IBD study (N = 35,289) was used as replication outcome. SNPs associated with bacteria abundance at the suggestive significance level (α = 1.0 × 10–5) were used as instrumental variables. Bacteria were grouped into families and genera.ResultsIn the discovery sample, a total of 30 features were available for analysis, including 15 families and 15 genera. Three features were nominally significant, including one family (Verrucomicrobiaceae, 2 IVs, beta = −0.04, p = 0.05) and two genera (Akkermansia, 2 IVs, beta = 0.04, p = 0.05; Dorea, 2 IVs, beta = −0.07, p = 0.04). All of them were successfully replicated in the replication sample (Verrucomicrobiaceae and Akkermansia Preplication = 0.02, Dorea Preplication = 0.01) with consistent effect direction.ConclusionWe identified specific pathogenic bacteria features that were causally associated with the risk of IBD, thus offering new insights into the prevention and diagnosis of IBD.

scholarly journals Vitamin D and Inflammatory Bowel Disease: Mendelian Randomization Analyses in the Copenhagen Studies and UK Biobank

2018 ◽  
Vol 103 (9) ◽  
pp. 3267-3277 ◽  
Author(s):  
Josephine Lund-Nielsen ◽  
Signe Vedel-Krogh ◽  
Camilla Jannie Kobylecki ◽  
Jørn Brynskov ◽  
Shoaib Afzal ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Vitamin D ◽  
Bowel Disease ◽  
Mendelian Randomization ◽  
Uk Biobank ◽  
Inflammatory Bowel

scholarly journals Causal Linkage Between Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Two-Sample Mendelian Randomization Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Ying Xie ◽  
Xuejie Chen ◽  
Minzi Deng ◽  
Yuhao Sun ◽  
Xiaoyan Wang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Primary Sclerosing Cholangitis ◽  
Bowel Disease ◽  
Sclerosing Cholangitis ◽  
Mendelian Randomization ◽  
Sensitivity Analyses ◽  
Genome Wide Association Studies ◽  
Causal Association ◽  
Statistical Heterogeneity ◽  
Inflammatory Bowel

BackgroundObservational studies suggest an association between inflammatory bowel disease (IBD) [including ulcerative colitis (UC) and Crohn’s disease (CD)] and Primary sclerosing cholangitis (PSC), but the causal association between the two diseases remains unclear.MethodsWe used two-sample Mendelian randomization (MR) to estimate the causal association between IBD and PSC. We chose single nucleotide polymorphisms (SNPs) data for analysis, obtained from previous genome-wide association studies (GWASs). Pleiotropy, heterogeneity, and sensitivity analyses were performed for quality control.ResultsWe found that the causal associations between IBD (both UC and CD) and PSC were significant (e.g., IBD and PSC, Robust adjusted profile score (RAPS) OR = 1.29, 95% CI 1.16∼1.44, p< 0.01; UC and PSC, RAPS OR = 1.40, 95% CI 1.23∼1.58, p< 0.01; CD and PSC, RAPS OR = 1.13, 95% CI 1.02∼1.26, p = 0.02). MR Egger, IVW, and ML tests found statistical heterogeneity between determined IV estimates. The leave-one-out analysis also indicated the sensitivity of the SNPs (e.g., IBD and PSC, MR-Egger Q = 644.30, p< 0.01; UC and PSC, MR-Egger Q = 378.30, p< 0.01; UC and PSC, MR-Egger Q = 538.50, p < 0.01).ConclusionMR analyses support the positive causal effect of IBD (including UC and CD) on PSC in a European population. We provide suggestions for preventing and treating the two diseases.

scholarly journals Assessment of Causal Relationship Between Rheumatoid Arthritis and Inflammatory Bowel Disease: A Bi-Directional Mendelian Randomization Study

2020 ◽  
Author(s):  
Xueer Zhang ◽  
Zhenhuang Zhuang ◽  
Jie Du ◽  
Wenxiu Wang ◽  
Ruotong Yang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Mendelian Randomization ◽  
Causal Relation ◽  
Weighted Median ◽  
Log Odds ◽  
Inflammatory Bowel ◽  
Summary Data ◽  
Gut Microbiota Composition

Abstract Objective: Observational studies have shown that rheumatoid arthritis (RA) was associated with a higher risk of inflammatory bowel disease (IBD), and vice versa. However, if such associations reflect causality remains unclear. We aimed to examine the bidirectional causal associations of RA with IBD, ulcerative colitis (UC), and Crohn’s disease (CD).Method: A Bi-directional Mendelian randomization (MR) analysis and Linkage Disequilibrium Score regression (LDSC) were used to investigate the causality between RA and IBD subtypes. Summary data was extracted from the Rheumatoid Arthritis Consortium International for Immunochip (RACI) consortium and the Genetics and Allied research in Rheumatic diseases Networking (GARNET) consortium (29,880 cases of RA and 73,758 controls); and the International IBD Genetics Consortium (38,155 cases of IBD and 48,485 controls; 17,647 cases of UC and 47,179 controls; 20,550 cases of CD and 41,642 controls). Results: Genetically predicted RA was associated with higher risks of IBD (per 1-unit higher log odds: odds ratio: 1.13; 95% confidence interval: 1.04-1.21; P=0.002) and UC (1.16; 1.07-1.25; P=1.5 × 10−4) after a Bonferroni correction (P<0.05/3). In addition, the weighted median method showed a suggestive association of RA with a higher risk of CD (1.16; 1.05-1.28; P=0.003). However, there was no evidence showing a causal relation of IBD, UC or CD with RA risk. Conclusion: Our findings provide novel evidence supporting a significant causality of RA with IBD or UC, whereas IBD is unlikely to increase the risk of RA, indicating the importance of keeping gut microbiota composition healthy for RA patients to prevent IBD.

scholarly journals Mendelian randomization study of inflammatory bowel disease and bone mineral density

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Fashuai Wu ◽  
Yu Huang ◽  
Jialu Hu ◽  
Zengwu Shao
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Summary Statistics ◽  
Inflammatory Bowel ◽  
Randomization Analysis

Abstract Background Recently, the association between inflammatory bowel disease (including ulcerative colitis and Crohn’s disease) and BMD has attracted great interest in the research community. However, the results of the published epidemiological observational studies on the relationship between inflammatory bowel disease and BMD are still inconclusive. Here, we performed a two-sample Mendelian randomization analysis to investigate the causal link between inflammatory bowel disease and level of BMD using publically available GWAS summary statistics. Methods A series of quality control steps were taken in our analysis to select eligible instrumental SNPs which were strongly associated with exposure. To make the conclusions more robust and reliable, we utilized several robust analytical methods (inverse-variance weighting, MR-PRESSO method, mode-based estimate method, weighted median, MR-Egger regression, and MR.RAPS method) that are based on different assumptions of two-sample MR analysis. The MR-Egger intercept test, Cochran’s Q test, and “leave-one-out” sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on BMD. Outlier variants identified by the MR-PRESSO outlier test were removed step-by-step to reduce heterogeneity and the effect of horizontal pleiotropy. Results Our two-sample Mendelian randomization analysis with two groups of exposure GWAS summary statistics and four groups of outcome GWAS summary statistics suggested a definitively causal effect of genetically predicted ulcerative colitis on TB-BMD and FA-BMD but not on FN-BMD or LS-BMD (after Bonferroni correction), and we merely determined a causal effect of Crohn’s disease on FN-BMD but not on the others, which was somewhat inconsistent with many published observational researches. The causal effect of inflammatory bowel disease on TB-BMD was significant and robust but not on FA-BMD, FN-BMD, and LS-BMD, which might result from the cumulative effect of ulcerative colitis and Crohn’s disease on BMDs. Conclusions Our Mendelian randomization analysis supported the causal effect of ulcerative colitis on TB-BMD and FA-BMD. As to Crohn’s disease, only the definitively causal effect of it on decreased FN-BMD was observed. Updated MR analysis is warranted to confirm our findings when a more advanced method to get less biased estimates and better precision or GWAS summary data with more ulcerative colitis and Crohn’s disease patients was available.

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