Associations between deep venous thrombosis and thyroid diseases: A two-sample bidirectional Mendelian Randomization study

Abstract

Backgrounds: In some previous observational studies, deep venous thrombosis (DVT) has been linked to thyroid diseases, but the findings are debatable. This study aimed to reveal whether some common thyroid diseases can causally result in DVT using the two-sample Mendelian Randomization (MR) approach. Methods We did a two-sample MR study that chose single nucleotide polymorphisms (SNPs) which are highly associated with some common thyroid diseases from the FinnGen datasets as our instruments, including autoimmune hyperthyroidism (962 cases and 172,976 controls), subacute thyroiditis (418 cases and 187,684 controls), hypothyroidism (26,342 cases and 59,827 controls) and malignant neoplasm of thyroid gland (989 cases and 217,803 controls). Outcomes datasets about deep venous thrombosis (6,767 cases and 330,392 controls) were obtained from the IEU open GWAS project. Inverse variance weighted (IVW), MR-Egger and weighted median were used to estimate the causal association between DVT and thyroid diseases. Cochran’s Q test was used to quantify the heterogeneity of instrumental variables. We also detected horizontal pleiotropy using MR-PRESSO. When the causal relationship was significant, a bidirectional Mendelian randomization analysis was performed to determine if there were reverse causal relationships between exposures and outcomes. Results The Mendelian Randomization analysis illustrated that autoimmune hyperthyroidism slightly raised the risk of DVT in IVW method[odds ratio (OR) = 1.000891; 95% confidence interval (CI):1.0001156–1.001667; p = 0.0243]. Weighted median showed a similar association[OR = 1.000984; 95%CI: 1.0000806–1.001888; p = 0.03278]. There was no evidence of heterogeneity in instrumental variables which Cochran’s Q test showed and MR-PRESSO didn’t assumed the presence of horizontal pleiotropy (p = 0.972). However, no evidence can point out that other thyroid diseases had relationship with DVT using the IVW method, weighted median method and MR-Egger regression. Conclusion Our research found that autoimmune hyperthyroidism may cause DVT. More evidences and lager samples are needed to draw more precise conclusions.