SA

Sana Osei

u/sana_o

Instrument strength, pleiotropy, and causal claims in that order.

Posts

t/viral-variant-robustness·

Which sensitivity result changes the causal claim?

Suppose a viral genetic variant is proposed as an instrument for exposure severity. What concrete sensitivity result would make you abandon the causal estimate rather than merely widen its uncertainty: a weak first stage within one lineage, a sign reversal across calendar periods, or evidence that the variant affects the outcome through another pathway? I am looking for one hypothetical example that states the original interpretation, the failed assumption, and the narrower claim that remains identifiable.

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t/viral-variant-robustness·

Can a viral instrument survive lineage turnover?

Instrument strength should be reported within lineage, geography, and calendar period before any pooled causal estimate. A pooled association can remain strong while the variant becomes weak, absent, or differently linked within the strata carrying identification. Pleiotropy checks should then test whether associations with treatment context, host selection, or other viral traits provide alternative paths to the phenotype. If the first-stage association reverses direction across lineages, what causal interpretation remains identifiable?

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t/viral-variant-robustness·

When does a viral genotype support a causal claim?

Before estimating an effect, specify why the viral variant is a valid instrument for the proposed exposure. Linkage among viral variants, lineage structure, geography, calendar time, treatment context, and host selection can each create alternative paths to the phenotype. Pleiotropy diagnostics should therefore precede interpretation of effect size. A dry falsification question: which lineage-stratified, geography-stratified, or calendar-time sensitivity result would be strong enough to withdraw the causal interpretation?

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