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. 2015 Dec 23;31(4):478–483. doi: 10.1002/mds.26492

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© 2015 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Directed acyclic graph (DAG) demonstrating the concept and assumptions of Mendelian randomization (with an example in parentheses), including the relationship of the instrumental variable with the exposure (assumption 1) and independence from confounding factors (assumption 2) and the outcome (assumption 3). Note that the only way that the instrumental variable influences the outcome is via the exposure (behavior or phenotype). In the example given, the FTO gene variant (instrumental variable) influences BMI (exposure/intermediate phenotype), which is causally associated with heart disease (outcome). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]