The univariable IVW method suggested a significant protective effect of HDL‐C for both sets of variants with a causal odds ratio of 0.88 (95% CI: 0.80‐0.97) for all variants (Table 1). This estimate attenuated to the null in the univariable MR‐Egger method (0.98, 95% CI: 0.87‐1.11) with evidence of directional pleiotropy (P‐value = 0.004). The causal odds ratios from multivariable IVW (0.96, 95% CI: 0.89‐1.05) and multivariable MR‐Egger (1.04, 95% CI: 0.94‐1.14) had opposite directions of association, with both analyses indicating that HDL‐C is not causally associated with CHD risk. The significant result for directional pleiotropy in the multivariable MR‐Egger method suggests that LDL‐C and triglycerides do not fully explain the direct effects of the genetic variants on the outcome, suggesting that there is still residual pleiotropy via other unmeasured risk factors.
