Pragmatic vs. naive genetic instrument selection in Mendelian randomization studies: a practical guide

Using default linkage disequilibrium parameters in Mendelian randomization can lead to suboptimal genetic instruments, affecting the validity of causal inferences.

• Why it matters: Accurate instrument selection is crucial for reliable MR results, yet many studies rely on default settings that may compromise instrument quality and study conclusions.
• What they did: The authors evaluated the impact of different LD clumping parameters and proposed a pragmatic framework based on empirical strength metrics to select genetic instruments more effectively.
• The result: Implementing this approach enhances the robustness and transparency of MR analyses, enabling more reliable causal inference across various exposure types.