Dataset Information

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

ABSTRACT:

Background

Recent 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 methods

MR 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 (? = 1.0 × 10^-5) were used as instrumental variables. Bacteria were grouped into families and genera.

Results

In 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 P _replication = 0.02, Dorea P _replication = 0.01) with consistent effect direction.

Conclusion

We 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.

SUBMITTER: Zhang ZJ

PROVIDER: S-EPMC7931927 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

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

Zhang Zi-Jia ZJ Qu Hong-Lei HL Zhao Na N Wang Jing J Wang Xiu-Yan XY Hai Rong R Li Bin B

Frontiers in genetics 20210218

<h4>Background</h4>Recent 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.<h4>Materials and methods</h4>MR analysis was performed on genome-wide association study (GWAS) summary statistics o ...[more]

PMID: 33679893

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Project description:IntroductionOver the past few years, multiple observational studies have speculated a potential association between inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), and osteoporosis. However, no consensus has been reached regarding their interdependence and pathogenesis. Herein, we sought to further explore the causal associations between them.MethodsWe validated the association between IBD and reduced bone mineral density in humans based on genome-wide association studies (GWAS) data. To investigate the causal relationship between IBD and osteoporosis, we performed a two-sample Mendelian randomization study using training and validation sets. Genetic variation data for IBD, CD, UC, and osteoporosis were derived from published genome-wide association studies in individuals of European ancestry. After a series of robust quality control steps, we included eligible instrumental variables (SNPs) significantly associated with exposure (IBD/CD/UC). We adopted five algorithms, including MR Egger, Weighted median, Inverse variance weighted, Simple mode, and Weighted mode, to infer the causal association between IBD and osteoporosis. In addition, we evaluated the robustness of Mendelian randomization analysis by heterogeneity test, pleiotropy test, leave-one-out sensitivity test, and multivariate Mendelian randomization.ResultsGenetically predicted CD was positively associated with osteoporosis risk, with ORs of 1.060 (95% CIs 1.016, 1.106; p = 0.007) and 1.044 (95% CIs 1.002, 1.088; p = 0.039) for CD in the training and validation sets, respectively. However, Mendelian randomization analysis did not reveal a significant causal relationship between UC and osteoporosis (p > 0.05). Furthermore, we found that overall IBD was associated with osteoporosis prediction, with ORs of 1.050 (95% CIs 0.999, 1.103; p = 0.055) and 1.063 (95% CIs 1.019, 1.109; p = 0.005) in the training and validation sets, respectively.ConclusionWe demonstrated the causal association between CD and osteoporosis, complementing the framework for genetic variants that predispose to autoimmune disease.

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Dataset Information

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

Background

Materials and methods

Results

Conclusion

Publications

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

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