Objective:

To review the principles, assumptions, and challenges of Mendelian randomization (MR) in infectious diseases, emphasizing the review aspect and its potential and limitations.

Key Findings:

• MR studies in infectious diseases have increased significantly, but many violate core assumptions, leading to unreliable results.
• Using infection as an exposure in MR studies is particularly challenging due to limited genetic variants and complex interactions, as seen in recent studies.
• Caution is needed when inferring causality from genetic variants associated with immune responses, particularly in the context of vaccination.

Interpretation:

While MR holds promise for causal inference in infectious diseases, careful consideration of its assumptions and limitations is crucial for valid conclusions, emphasizing the need for rigorous analysis.

Limitations:

• Many MR studies do not adequately address the limitations of their analyses, often overlooking critical assumptions.
• The complexity of genetic influences on infection makes it difficult to establish clear causal relationships, as demonstrated in various studies.

Conclusion:

Mendelian randomization can provide unique insights into infectious diseases, but its application must be approached with caution to avoid misleading results, reinforcing the need for careful methodological considerations.