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Trimethylamine N-oxide and risk of inflammatory bowel disease: A Mendelian randomization study.

ABSTRACT: A previous study suggested that inflammatory bowel disease (IBD) patients have low plasma levels of trimethylamine N-oxide (TMAO). In the present study, we examined this hypothesis using Mendelian randomization analysis. We used summary statistics data for single-nucleotide polymorphisms associated with plasma levels of TMAO, and the corresponding data for IBD from a genome-wide association meta-analysis of 59,957 individuals (25,042 diagnosed IBD cases, 34,915 controls). The association between genetically predicted plasma TMAO levels and IBD showed odds ratios (95% confidence interval [CI]) per 1 interquartile range increment (per 2.4 μmol/L) in TMAO levels were 0.91 (0.81-1.01, P = .084) for IBD, 0.88 (0.76-1.02, P = .089) for ulcerative colitis, 0.91 (0.79-1.05, P = .210) for Crohn disease. There was no evidence for pleiotropy based on the Mendelian randomization-Egger regression analyses (P-intercept = 0.669 for IBD). Further investigations would be needed to understand the causal relationship between TMAO and IBD.

SUBMITTER: Banno Y

PROVIDER: S-EPMC10470767 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Trimethylamine N-oxide and risk of inflammatory bowel disease: A Mendelian randomization study.

Banno Yukika Y Nomura Miho M Hara Risako R Asami Momoko M Tanaka Kotone K Mukai Yuuka Y Tomata Yasutake Y

Medicine 20230801 34

A previous study suggested that inflammatory bowel disease (IBD) patients have low plasma levels of trimethylamine N-oxide (TMAO). In the present study, we examined this hypothesis using Mendelian randomization analysis. We used summary statistics data for single-nucleotide polymorphisms associated with plasma levels of TMAO, and the corresponding data for IBD from a genome-wide association meta-analysis of 59,957 individuals (25,042 diagnosed IBD cases, 34,915 controls). The association between ...[more]

PMID: 37653747

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Project description:BackgroundThe causal genetic relationship between common parenteral manifestations of inflammatory bowel disease (IBD) and urolithiasis remains unclear because their timing is difficult to determine. This study investigated the causal genetic association between IBD and urolithiasis using Mendelian randomization (MR) based on data from large population-based genome-wide association studies (GWASs).MethodsA two-sample MR analysis was performed to assess the potential relationship between IBD and urolithiasis. Specific single nucleotide polymorphism data were obtained from GWASs, including IBD (n = 59957) and its main subtypes, Crohn's disease (CD) (n = 40266) and ulcerative colitis (UC) (n = 45975). Summarized data on urolithiasis (n = 218792) were obtained from different GWAS studies. A random-effects model was analyzed using inverse-variance weighting, MR-Egger, and weighted medians.ResultsGenetic predisposition to IBD and the risk of urolithiasis were significantly associated [odds ratio (OR), 1.04 (95% confidence interval [CI], 1.00-.08), P = 0.01]. Consistently, the weighted median method yielded similar results [OR, 1.06 (95% CI, 1.00-1.12), P = 0.02]. The MR-Egger method also demonstrated comparable findings [OR, 1.02 (95% CI, 0.96-1.08), P = 0.45]. Both funnel plots and MR-Egger intercepts indicated no directional pleiotropic effects between IBD and urolithiasis. CD was strongly associated with it in its subtype analysis [OR, 1.04 (95% CI, 1.01-1.07), P = 0.01], and UC was also causally associated with urolithiasis, although the association was not significant [OR, 0.99 (95% CI, 0.95-1.03), P = 0.71].ConclusionA unidirectional positive causal correlation was identified between IBD and urolithiasis, with varying degrees of association observed among the different subtypes of IBD. Recognizing the increased incidence of urolithiasis in patients with IBD is crucial in clinical practice. Early detection and surveillance of IBD, improved patient awareness, adoption of preventive strategies, and promotion of collaborative efforts among healthcare providers regarding treatment methodologies are vital for improving patient outcomes.

Dataset Information

Trimethylamine N-oxide and risk of inflammatory bowel disease: A Mendelian randomization study.

Publications

Trimethylamine N-oxide and risk of inflammatory bowel disease: A Mendelian randomization study.

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