Thyroid dysfunction and pulmonary arterial hypertension: A bidirectional mendelian randomization study.

Objective: Thyroid dysfunction can cause several cardiovascular diseases. Studies have suggested a link between thyroid dysfunction and an increased risk of Pulmonary Arterial Hypertension (PAH). However, the causal association between this link is unknown. The aim of this study was to investigate the causal association between thyroid dysfunction and PAH using bidirectional two-sample Mendelian Randomization (MR) analysis. Method: Thyroid dysfunction (Free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), hyperthyroidism and hypothyroidism) and PAH were respectively used as exposure and outcome factors. The bidirectional causal association between thyroid dysfunction and PAH was analyzed by using Inverse Variance Weighting (IVW), MR-Egger regression (MR-Egger), and Weighted Median (WM) methods. Cochran's Q test was used to analyze the heterogeneity among single nucleotide polymorphisms (SNPs). The intercept term of MR-Egger regression and MR-PRESSO were used to analyze horizontal pleiotropy. The effect of single SNP on the MR analysis results was analyzed by leave-one-out method. Results: The IVW showed that hypothyroidism could increase the risk of PAH (OR = 1.485, 95 % CI [1.051, 2.100], P = 0.025), while FT3, FT4, TSH and hyperthyroidism were not associated with the risk of PAH. Furthermore, we found no evidence of reverse causal association between PAH and thyroid dysfunction. Conclusion: Our study found that hypothyroidism is causally associated with an increased risk of PAH. However, further investigations are still needed to illustrate the connection between thyroid dysfunction and PAH.