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

Area of Science:

• Genetics
• Reproductive Health
• Endocrinology

Background:

• Observational studies suggest a link between preeclampsia (PE) and thyroid disease, but causality is unproven.
• Assessing the causal relationship between PE and various thyroid conditions is crucial for understanding disease mechanisms.

Purpose of the Study:

• To investigate the potential causal associations between preeclampsia and five thyroid diseases: thyroid cancer, hypothyroidism, hyperthyroidism, Graves' disease, and Hashimoto thyroiditis.
• To examine the reverse causality, determining if PE causally affects these thyroid conditions.

Main Methods:

• A two-sample bidirectional Mendelian randomization (MR) study utilized genome-wide association study summary statistics.
• Included large cohorts for PE, thyroid cancer, hypothyroidism, hyperthyroidism, Graves' disease, and Hashimoto thyroiditis.
• Employed inverse variance weighted methods and sensitivity analyses (MR-Egger, weighted median, leave-one-out, Cochran's Q, MR-Egger intercept) to ensure robust findings.

Main Results:

• Genetic liability to hypothyroidism, hyperthyroidism, Graves' disease, and Hashimoto thyroiditis showed a significant association with increased PE risk.
• Odds ratios (ORs) indicated a positive association: hypothyroidism (OR 1.06), hyperthyroidism (OR 1.06), Graves' disease (OR 1.06), and Hashimoto thyroiditis (OR 1.10).
• No significant causal link was found between thyroid cancer and PE, nor did PE causally influence any of the studied thyroid diseases.

Conclusions:

• Evidence supports a causal relationship between hypothyroidism, hyperthyroidism, Graves' disease, Hashimoto thyroiditis, and preeclampsia.
• No causal association was detected between thyroid cancer and preeclampsia.
• Preeclampsia does not exert a causal effect on the investigated thyroid diseases.