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. 2021 Nov 8;21:532. doi: 10.1186/s12872-021-02342-6

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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 — Assumptions of a Mendelian randomization analysis and data sources. Mendelian randomization analysis rests on 3 assumptions. First, the genetic instruments used as instrumental variables are strongly predictive of exposure (this study specifically refers to n-3 PUFAs, Assumption 1). Second, the association of genetic instruments with outcome (for example, IHD in this study) is not confounded by measured or unmeasured factors (Assumption 2). Third, the effect of the genetic instrument on outcome (IHD) should be fully mediated via exposure (n-3 PUFAs) and not through any direct or alternative causal pathways (Assumption 3). ALA α-linolenic acid, DHA docosahexaenoic acid, DIAGRAM DIAbetes Genetics Replication and Meta-analysis, DPA docosapentaenoic acid, EPA eicosapentaenoic acid, GIANT Genetic Investigation of Anthropometric Traits, GLGC Global Lipids Genetics Consortium, GWAS genome-wide association studies, ICBP International Consortium for Blood Pressure, IHD ischemic heart disease, PUFAs polyunsaturated fatty acids, SNP single nucleotide polymorphism