Fig. 4: Using MR within the Empareg trial emulation to identify confounders.
a, A DAG illustrating the relationship between treatment initiation (X) and trial outcome (Y), as well as the effect of a genetic instrument (G) of a confounding variable (C) on both the treatment initiation and trial outcome, only through the confounding variable. b, Results of an MR analysis using IVW as a statistical test to study the causal effects of 18 traits on CHD, representing the trial outcome, and empagliflozin, representing the treatment initiation. Left: MR for association between 18 traits on coronary artery disease using two-sample MR. Middle: MR for association between 18 traits on empagliflozin initiation in the full study population. Right: MR for association between 18 traits on empagliflozin initiation after applying the RCT’s eligibility criteria. The point estimates represent the ORs with lines representing their 95% CI. For continuous confounders, the OR reflects the change in the outcome variable associated with a 1 s.d. increase in the exposure variable; for binary confounders, the OR represents the change in the outcome variable when comparing the presence versus the absence of the binary exposure. A circle around the point estimates represents statistical significance with a P value threshold of 5 × 10−2. A square around the point estimate represents statistical significance with a P value threshold of 2.8 × 10−3. Single asterisk represents putative confounder due to significance in left and middle panels of b; double asterisks represent putative confounder due to significance in left and right panels of b. Elig. crit., eligibility criteria.
