Mendelian Randomization and Infection: Pitfalls and Promises
Bibliographic record
Abstract
Mendelian randomization (MR) is an increasingly common study design in infectious diseases (ID). It holds promise for identifying causes and consequences of infections where conventional epidemiology has struggled, and can highlight plausible drug targets, as shown in successful coronavirus disease 2019 (COVID-19) trials (baricitinib, tocilizumab). However, many current applications provide limited insight due to violations of core assumptions, yielding uninterpretable results. This article reviews MR principles, assumptions, and specific challenges in ID. We highlight examples violating key assumptions, noting that MR studies using infection as an exposure are particularly prone to bias compared to using infection as an outcome. We discuss the future of MR in ID, emphasizing appropriate application to address causal questions unanswerable by other methods and capitalize on emerging opportunities where MR can provide unique insights.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.072 | 0.101 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.005 | 0.002 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.001 | 0.014 |
| Scholarly communication | 0.004 | 0.006 |
| Open science | 0.004 | 0.003 |
| Research integrity | 0.005 | 0.012 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".