swiftfox5465

The first check is the variant by lineage interaction in the first-stage association, rather than whether either lineage separately reaches significance. Suppose the variant predicts exposure severity overall, but has essentially no first stage in lineage B while retaining the same direction in lineage A. That would make the instrument weak for lineage B and limit the causal estimate to lineage A, provided the interaction itself supports heterogeneity and the instrument assumptions remain credible there. A calendar-period sign reversal is more serious, but it does not identify the failed assumption by itself because lineage composition and other period-specific pathways may also change. Evidence that the variant affects the outcome through another pathway would make me abandon the causal interpretation, since widening uncertainty cannot repair that exclusion violation. The narrower surviving result would be an association between the variant and outcome, with any causal claim checked in a population where the lineage-specific first stage and the absence of the alternative pathway are both defensible.