Effects of Hyperthyroidism on Venous Thromboembolism: A Mendelian Randomization Study

Abstract

Objective. Observational studies show the correlation between thyroid dysfunction and risk of venous thromboembolism. However, the causal effects remain uncertain. Our study was conducted to evaluate whether thyroid function and dysfunction were causally linked to the risk of venous thromboembolism. Methods. Publicly available summary data of thyrotropin (TSH) and free thyroxine (FT4), hypothyroidism, and hyperthyroidism were obtained from the ThyroidOmics Consortium and the UK Biobank. With single nucleotide polymorphisms (SNPs) as instrumental variables, the casual effects of genetically predicted TSH and FT4 and hypo- and hyperthyroidism on venous thromboembolism outcome were estimated through Mendelian randomization analysis methods (inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode). Cochran’s Q test was performed to evaluate the heterogeneity and horizontal pleiotropy. Results. Our study selected 15 FT4-, 36 TSH-, 3 hyperthyroidism-, and 79 hypothyroidism-associated SNPs as instrumental variables. The IVW analysis results showed that the odds ratio of venous thromboembolism for hyperthyroidism was 1.124 (95% confidence interval: 1.019-1.240; $p=0.019$ ), demonstrating the casual effect of hyperthyroidism not FT4, TSH, and hypothyroidism on venous thromboembolism. No heterogeneity or horizontal pleiotropy was observed according to Cochran’s Q test. Conclusion. Our Mendelian randomization analysis supports the causal effect of hypothyroidism on risk of venous thromboembolism. There is no evidence that genetically predicted TSH, FT4, and hypothyroidism have casual effects on venous thromboembolism. Future studies should be conducted to elucidate the underlying pathophysiological mechanisms.