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. 2021 Jun 21;13:104. doi: 10.1186/s13073-021-00914-x

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© The Author(s) 2021

Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — Flow chart of study design. A Cardio-metabolic traits were body mass index (BMI), type 2 diabetes (T2D), C-reactive protein (CRP), lipoprotein (HDL-C), low-density lipoprotein (LDL-C), total cholesterol (TC), triglycerides (TG), systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and coronary artery disease (CAD). Tested lung function traits were first second forced expiratory capacity (FEV1), forced vital capacity (FVC) and a ratio of both FEV1/FVC. B Graphical relationship diagrams in a classical MR and mediation analysis. Upper panel gives overview of MR analysis, indicating the use of genetic instruments instead of the actual exposure. Arrow labelled with C in upper panel refers to the causal estimate as well as the C-path in mediation analysis setting. Lower panel gives an overview of the mediation analysis following Baron-Kenney approach. For mediation analysis in this study, we subtracted C’ path from C-path to get effect sizes for mediation