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. 2019 Jun 28;9:9386. doi: 10.1038/s41598-019-45747-2

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Directed Acyclic Graph. This figure displays the MR study design. Confounders are that are factors associated with both IL18 level and risk of IBD, yet do not lie in the causal pathway between IL18 and IBD. When confounding factors are unknown, or not adequately adjusted for in observational analyses, they bias estimates of the association between IL18 and IBD. In MR analyses, SNPs that influence IL18 level are tested for their effect on IBD instead of IL18 measurements. Since SNPs are randomized at conception, this breaks association with potentially confounding variables and allows for an estimate of the effect on IL18 on IBD risk.