Assessment of causal direction between thyroid function and cardiometabolic health: a Mendelian randomization study

Jing-Jia Wang; Zhen-Huang Zhuang; Can-Qing Yu; Wen-Yao Wang; Wen-Xiu Wang; Kuo Zhang; Xiang-Bin Meng; Jun Gao; Jian Tian; Ji-Lin Zheng; Jie Yang; Tao Huang; Chun-Li Shao; Yi-Da Tang

doi:10.11909/j.issn.1671-5411.2022.01.004

Assessment of causal direction between thyroid function and cardiometabolic health: a Mendelian randomization study

J Geriatr Cardiol. 2022 Jan 28;19(1):61-70. doi: 10.11909/j.issn.1671-5411.2022.01.004.

Authors

Jing-Jia Wang¹, Zhen-Huang Zhuang^{2

3}, Can-Qing Yu^{2

3}, Wen-Yao Wang¹, Wen-Xiu Wang^{2

3}, Kuo Zhang¹, Xiang-Bin Meng⁴, Jun Gao⁴, Jian Tian¹, Ji-Lin Zheng¹, Jie Yang¹, Tao Huang^{2

3

5}, Chun-Li Shao⁴, Yi-Da Tang⁴

Affiliations

¹ Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing, China.
³ Center for Intelligent Public Health, Academy for Artificial Intelligence, Peking University, Beijing, China.
⁴ Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China.
⁵ Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, Beijing, China.

PMID: 35233224
PMCID: PMC8832047
DOI: 10.11909/j.issn.1671-5411.2022.01.004

Abstract

Background: Growing evidence have demonstrated that thyroid hormones have been involved in the processes of cardiovascular metabolism. However, the causal relationship of thyroid function and cardiometabolic health remains partly unknown.

Methods: The Mendelian randomization (MR) was used to test genetic, potentially causal relationships between instrumental variables and cardiometabolic traits. Genetic variants of free thyroxine (FT4) and thyrotropin (TSH) levels within the reference range were used as instrumental variables. Data for genetic associations with cardiometabolic diseases were acquired from the genome-wide association studies of the FinnGen, CARDIoGRAM and CARDIoGRAMplusC4D, CHARGE, and MEGASTROKE. This study was conducted using summary statistic data from large, previously described cohorts. Association between thyroid function and essential hypertension (EHTN), secondary hypertension (SHTN), hyperlipidemia (HPL), type 2 diabetes mellitus (T2DM), ischemic heart disease (IHD), myocardial infarction (MI), heart failure (HF), pulmonary heart disease (PHD), stroke, and non-rheumatic valve disease (NRVD) were examined.

Results: Genetically predicted FT4 levels were associated with SHTN (odds ratio = 0.48; 95% CI = 0.04-0.82,P = 0.027), HPL (odds ratio = 0.67; 95% CI = 0.18-0.88,P = 0.023), T2DM (odds ratio = 0.80; 95% CI = 0.42-0.86,P = 0.005), IHD (odds ratio = 0.85; 95% CI = 0.49-0.98,P = 0.039), NRVD (odds ratio = 0.75; 95% CI = 0.27-0.97,P = 0.039). Additionally, genetically predicted TSH levels were associated with HF (odds ratio = 0.82; 95% CI = 0.68-0.99,P = 0.042), PHD (odds ratio = 0.75; 95% CI = 0.32-0.82,P = 0.006), stroke (odds ratio = 0.95; 95% CI = 0.81-0.97,P = 0.007). However, genetically predicted thyroid function traits were not associated with EHTN and MI.

Conclusions: Our study suggests FT4 and TSH are associated with cardiometabolic diseases, underscoring the importance of the pituitary-thyroid-cardiac axis in cardiometabolic health susceptibility.

Copyright and License information: Journal of Geriatric Cardiology 2022.