Figure 1.

Schematic representation of MR. (A) Mendelian randomization can be used to test the hypothesis that trait A causes trait B, provided that conditions (1), (2) and (3) are met adequately, governing that Z_A is a valid instrument, in that (1) it is associated with the intermediate phenotype of interest; (2) has no association with the outcome except through the intermediate phenotype, and (3) is not related to measured or unmeasured confounding factors. (B). In bi-directional MR, the causal direction between traits (A and B) (if any) can be elucidated, if valid instruments are present for each trait.