Sun, Y;
Chen, X;
Wang, S;
Deng, M;
Xie, Y;
Wang, X;
Chen, J;
(2021)
Gluten-free Diet Reduces the Risk of Irritable Bowel Syndrome: A Mendelian Randomization Analysis.
Frontiers in Genetics
, 12
, Article 684535. 10.3389/fgene.2021.684535.
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Abstract
Background: Whether a gluten-free diet (GFD) is a cause of irritable bowel syndrome (IBS) remains controversial. We aim at exploring the causal relationship between gluten intake and IBS within Mendelian randomization (MR) design. Methods: We conducted a two-sample MR and selected single-nucleotide polymorphisms (SNPs) associated with GFD as instrumental variables (IVs). SNPs and genetic associations with GFD and IBS were obtained from the latest genome-wide association studies (GWAS) in Europeans (GFD: cases: 1,376; controls: 63,573; IBS: cases:1,121; controls: 360,073). We performed inverse variance weighting (IVW) as the primary method with several sensitivity analyses like MR-Egger and MR-PRESSO for quality control. The above analyses were re-run using another large dataset of IBS, as well as changing the p-value threshold when screening IVs, to verify the stability of the results. Results: The final estimate indicated significant causal association [per one copy of effect allele predicted log odds ratio (OR) change in GFD intake: OR = 0.97, 95% confidence interval (CI) 0.96 to 0.99, p < 0.01] without heterogeneity statistically (Q = 2.48, p = 0.78) nor horizontal pleiotropy biasing the causality (p = 0.92). Consistent results were found in validation analyses. Results of MR Steiger directionality test indicated the accuracy of our estimate of the causal direction (Steiger p < 0.001). Conclusion: GFD might be a protective factor of IBS. Therefore, we suggest taking a diet of lower gluten intake into account in IBS prevention and clinical practice.
| Type: | Article |
|---|---|
| Title: | Gluten-free Diet Reduces the Risk of Irritable Bowel Syndrome: A Mendelian Randomization Analysis |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fgene.2021.684535 |
| Publisher version: | https://doi.org/10.3389/fgene.2021.684535 |
| Language: | English |
| Additional information: | © 2021 Sun, Chen, Wang, Deng, Xie, Wang, Chen and Hesketh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | causal association, genome-wide association studies, gluten-free diet, irritable bowel syndrome, mendelian randomization |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10140747 |
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