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Illustration of the instrumental variable (IV) assumptions for univariate Mendelian randomization as diagrammed by a directed acyclic graph. To be a valid IV, a genetic variant G must be (1) associated with the exposure X, (2) independent of possible confounders U, and (3) not be associated with the outcome Y directly. The three IV assumptions are annotated accordingly, with dotted lines representing violations of the second and third assumptions.
