Thyroid disorders as potential causal factors for preeclampsia: A two-sample bidirectional mendelian randomization study.

Background: Although clinical observational studies have reported a connection between preeclampsia (PE) and thyroid disease, the underlying causality remains unclear. The study aims to assess the potential causality between PE and thyroid disease.

Methods: A two-sample bidirectional Mendelian randomization (MR) study was conducted using the summary statistics from the genome-wide association studies on PE (128 668 individuals), thyroid cancer (407 746 individuals), hypothyroidism (410 141 individuals), hyperthyroidism (460 499 individuals), Graves' disease (458 620 individuals), and Hashimoto thyroiditis (395 640 individuals). The inverse variance weighted approach was used as the main method. Additionally, we performed multiple method analyses, including MR-Egger, simple mode, weighted median, and weighted mode tests to extensively examine our results. Furthermore, we conducted sensitivity analyses such as the leave-one-out test, Cochran's Q test, and the MR-Egger intercept test to evaluate the reliability and stability of our findings.

Results: The MR analysis revealed that genetic susceptibility to hypothyroidism, hyperthyroidism, Graves' disease and Hashimoto thyroiditis was significantly associated with PE. The odds ratios (ORs) for them were as follows: hypothyroidism: OR 1.06 (95% confidence interval [CI], 1.00-1.12; P = 0.031); hyperthyroidism: OR 1.06 (95% CI, 1.00-1.13; P = 0.049), Graves' disease: OR 1.06 (95% CI, 1.01-1.10; P = 0.008); Hashimoto thyroiditis: OR 1.10 (95% CI, 1.03-1.17; P = 0.003). However, there was no statistically significant association between thyroid cancer and PE (P > 0.05). A reverse MR analysis indicated that genetically predicted PE was not statistically significantly associated with these five thyroid diseases (P > 0.05). Our sensitivity analyses demonstrated the absence of significant horizontal pleiotropy, ensuring the stability and reliability of our findings.

Conclusions: Our study suggests a causality between hypothyroidism, hyperthyroidism, Graves' disease, Hashimoto thyroiditis and PE. However, no statistically significant association was found between thyroid cancer and PE. Conversely, PE did not show a causal effect on any of these five thyroid diseases.