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. 2019 Apr 5;10:1561. doi: 10.1038/s41467-019-09381-w

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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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Fig. 1 — Directed acyclic graph of association of SNP G with prognosis Y conditional on incidence X. U is a composite variable including all common causes of X and Y, and may include polygenic effects as well as non-genetic risk factors. In our examples, X is idiopathic pulmonary fibrosis or Crohn’s disease, and Y is survival or prognosis. Conditioning on X induces the moralised association between G with U shown by the dotted line. This creates association between G and Y via the path $G - U \to Y$ in addition to the direct effect G $\to$ Y