Assessment of causal association between thyroid function and lipid metabolism: a Mendelian randomization study.

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

Journal: Chinese medical journal 2021;134(9):1064-1069

PMID: 33942801

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Plain Language Summary

Obesity, dyslipidaemia, and metabolic syndrome are major risk factors for cardiovascular disease, however, effect of thyroid dysfunction on dyslipidaemia and cardiovascular disease is largely unknown. This study used mendelian randomisation (MR), where a genetic variant is used as an instrumental variable to detect the causal effects of exposure to disease. This study used two sample MR analyses to find out whether clinical thyroid function measures show a causal relationship with the changes in lipid levels. The results showed a significant association between the elevated thyrotropin (TSH) level and increased total cholesterol. Also, there was a significant correlation between the free triiodothyronine (FT3): free thyroxine (FT4) ratio and total cholesterol and low-density lipoprotein (LDL). Further robust studies are required to confirm the results and investigate the causal effect of thyroid hormone dysregulation and cardiometabolic diseases due to the limitations of this study. However, healthcare professionals can use the results of this study to understand the importance of the pituitary-thyroid-cardiac axis in lipid metabolism and its impact on cardiometabolic health.

Abstract

BACKGROUND

Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR).

METHODS

The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism.

RESULTS

The results demonstrated that increased TSH levels were significantly associated with higher TC (β = 0.052, P = 0.002) and LDL (β = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (β = 0.240, P = 0.033) and LDL (β = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids.

CONCLUSION

Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.

Address: 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 100037, China.; Department of Epidemiology & Biostatistics, School of Public Health, Peking University, Beijing 100191, China.; Center for Intelligent Public Health, Academy for Artificial Intelligence, Peking University, Beijing 100191, China.; Department of Cardiology, Zhengzhou University People's Hospital, Central China Fuwai Hospital, Central China Branch of the National Cardiovascular Center, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China.; Department of Cardiology, First Affiliated Hospital of Hebei Medical University, Hebei 050031, China.; Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, Beijing 100191, China.; Department of Cardiology, Peking University Third Hospital, Beijing 100191, China.

DOI: 10.1097/CM9.0000000000001505