Mendelian randomization is a crucial tool in medical research for understanding disease causation. It uses genetic variations as “natural experiments” to determine cause-and-effect relationships. The choice of genetic variations is vital for accurate results, with a focus on biologically motivated approaches to select genes directly related to the exposure. Genome-wide analyses, while tempting due to their vast data, can introduce noise and weaken the signal, leading to unreliable conclusions. However, they can still provide supporting evidence when used cautiously. Combining biological understanding with statistical expertise is essential for drawing accurate causal conclusions from Mendelian randomization, ensuring a better understanding of disease causes.
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Prioritizing biologically motivated approaches in Mendelian randomization studies
