Causal Association of Free Triiodothyronine Level with Ischemic Stroke Outcome: A Mendelian Randomization Study

The global burden of ischemic stroke requires a search for new factors that affect its risk and outcomes. Recent studies have shown that triiodothyronine could potentiate favorable stroke outcomes, but the reason for this is still unclear. To clarify the effects of the free triiodothyronine (fT3) level on stroke outcomes, we adopted a Mendelian randomization (MR) approach to evaluate their causal relationship. The genetic variants associated with the free triiodothyronine (fT3) level were obtained from the ThyroidOmics Consortium. Thirteen single-nucleotide polymorphisms, genetically predicting the fT3 level with a significance of p < 10^-7, were adopted for MR analysis. Summary-level data for ischemic stroke outcomes (reported as a continuous variable, namely the modified Rankin score 3 months after stroke) was obtained from the GISCOME network. MR analyses were performed using the TwoSampleMR framework. The inverse-variance weighting method of MR analysis showed that a genetically predicted increase in fT3 level is associated with a reduction in ordinal Modified Rankin Scale scores (OR = 0.581, 95% CI 0.37-0.92, p = 0.0183). This study showed that higher fT3 levels could be causally associated with more favorable ischemic stroke outcomes and provides more evidence for the possibility of using thyroid hormone (TH) analogs to improve stroke outcomes.