Related Experiment Videos
Thyroid function and hypertensive disorders of pregnancy: Insights from a sex-specific cohort study, Mendelian
Yu He1, Yeshen Zhang1,2, Yanxin Sun3,4
1Department of Cardiology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Objective:
To investigate the association of a history of hypertensive disorders of pregnancy (HDP) and a higher risk of cardiovascular disease using a sex-specific cohort study, bidirectional two-sample Mendelian randomization (MR), and in vitro experiments.
Methods:
Multivariable logistic regression was used to assess the association between thyroid function and HDP. We performed bidirectional two-sample MR using summary statistics from genome-wide association study meta-analyses, FinnGen, and UKB to assess the potential association between thyroid function and HDP. In vitro experiments were conducted to explore the potential biologic mechanisms underlying the observed association.
Results:
In the cohort (n = 119 668), hyperthyroidism was associated with higher HDP risk (odds ratio [OR] 1.79, 95% confidfence interval [CI] 1.10-2.92, P = 0.020; fully adjusted for confounders). MR identified a potential association of genetically predicted thyroid-stimulating hormone (TSH) on HDP (OR 0.92, 95% CI 0.85-0.99, P = 0.018), but no evidence was found to support a causal effect of hypothyroidism, hyperthyroidism, or free thyroxine on HDP. Reverse MR indicated that genetically predicted pre-eclampsia was associated with elevated TSH levels (β 0.12, 95% CI 0.05-0.19, P < 0.001). In vitro experiments confirmed and provided supportive mechanistic evidence that TSH may directly induce vascular endothelial injury and dysfunction.
Conclusion:
This study demonstrates an independent observational association between hyperthyroidism and an increased risk of HDP, and provides supportive genetic evidence for a possible bidirectional association between genetically predicted TSH and HDP. These findings highlight TSH as a potential biomarker for HDP risk stratification.
Related Concept Videos
Hypertension III: Clinical Manifestations and Diagnostic Studies
Hyperthyroidism II: Pathophysiology
Regression Toward the Mean
Hypertension and Regulation of Blood Pressure
Hypertension IV: Drug Therapy and Lifestyle Modifications
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase