Effects of Hyperthyroidism on Venous Thromboembolism: A Mendelian Randomization Study

Area of Science:

• Endocrinology
• Genetics
• Cardiovascular Medicine

Background:

• Observational studies suggest a correlation between thyroid dysfunction and venous thromboembolism (VTE).
• The causal relationship between thyroid function/dysfunction and VTE risk remains unclear.
• This study aims to clarify the causal link using genetic data.

Purpose of the Study:

• To investigate the causal effect of thyroid function (TSH, FT4) and dysfunction (hypothyroidism, hyperthyroidism) on the risk of venous thromboembolism.
• To differentiate causal associations from mere correlations.

Main Methods:

• Utilized Mendelian randomization analysis with summary data from ThyroidOmics Consortium and UK Biobank.
• Employed single nucleotide polymorphisms (SNPs) as instrumental variables for TSH, FT4, hypothyroidism, and hyperthyroidism.
• Applied inverse variance weighted (IVW), MR-Egger, and weighted median methods, assessing heterogeneity and pleiotropy with Cochran's Q test.

Main Results:

• Hyperthyroidism showed a causal effect on venous thromboembolism risk (OR 1.124, 95% CI 1.019-1.240, p=0.019).
• No causal effect was observed for TSH, FT4, or hypothyroidism on venous thromboembolism.
• Cochran's Q test indicated no significant heterogeneity or horizontal pleiotropy.

Conclusions:

• Mendelian randomization analysis supports a causal relationship between hyperthyroidism and venous thromboembolism.
• Genetic prediction of TSH, FT4, and hypothyroidism does not demonstrate a causal effect on venous thromboembolism.
• Further research is needed to explore the pathophysiological mechanisms underlying hyperthyroidism-associated VTE.