A Causal Relationship Between Hypothyroidism and Gestational Hypertension: Results From a Two-Sample Mendelian Randomization Analysis

Aims/Background Although hypothyroidism induced thyroid hormone disorders affect cardiovascular system homeostasis, whether hypothyroidism has a causal effect on gestational hypertension remains unknown. Therefore, our research aims to explore the causal relationship between hypothyroidism and gestational hypertension using Mendelian randomization (MR) analysis. Methods Summary data genome-wide association study of hypothyroidism (30,155 cases and 379,986 controls in the discovery dataset; 26,342 cases and 59,827 controls in the replicated dataset) and gestational hypertension (14,727 cases and 196,143 controls) were used for analysis. Inverse-variance weighted (IVW), weighted median, weighted mode and MR-Egger methods were used to estimate the causality between hypothyroidism and gestational hypertension. Results Hypothyroidism significantly increased the risk of gestational hypertension, as indicated by IVW (odds ratio (OR) = 1.0433, 95% confidence interval (CI) = 1.0081-1.0798, p = 0.0155), MR Egger (OR = 1.1445, 95% CI = 1.0620-1.2334, p = 0.0008), weighted median (OR = 1.0802, 95% CI = 1.0204-1.1435, p = 0.0079) and weighted mode (OR = 1.0999, 95% CI = 1.0286-1.1761, p = 0.0071) in the discovery analysis, which was consistent with the results of the replicated analysis. There was no bidirectional causality for hypothyroidism or gestational hypertension in the reverse MR analysis. Conclusion Our findings highlight the importance of hypothyroidism induced thyroid hormone disorder in increasing the risk of gestational hypertension by affecting cardiovascular system homeostasis. Early intervention in patients with hypothyroidism might reduce the risk of gestational hypertension and maternal and neonatal morbidity and mortality. Further studies are needed to determine the relationship between these factors and the underlying mechanism in detail.