Variation in Normal Range Thyroid Function Affects Serum Cholesterol Levels, Blood Pressure, and Type 2 Diabetes Risk: A Mendelian Randomization Study

Aleksander Kuś*, Eirini Marouli, Fabiola Del Greco M., Layal Chaker, Tomasz Bednarczuk, Robin P. Peeters, Alexander Teumer, Marco Medici, Panos Deloukas

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Scopus)


Background: Observational studies have demonstrated that variation in normal range thyroid function is associated with major cardiovascular risk factors, including dyslipidemia, hypertension, type 2 diabetes (T2D), and obesity. As observational studies are prone to residual confounding, reverse causality, and selection bias, we used a Mendelian randomization (MR) approach to investigate whether these associations are causal or not. Methods: Two-sample MR analysis using data from the largest available genome-wide association studies on normal range thyrotropin (TSH) and free thyroxine (fT4) levels, serum lipid levels, blood pressure measurements, T2D, and obesity traits (body mass index [BMI] and waist/hip ratio). Results: A one standard deviation (SD) increase in genetically predicted TSH levels was associated with a 0.037 SD increase in total cholesterol levels (p = 3.0 × 10-4). After excluding pleiotropic instruments, we also observed significant associations between TSH levels and low-density lipoprotein levels (β = 0.026 SD, p = 1.9 × 10-3), pulse pressure (β =-0.477 mmHg, p = 7.5 × 10-10), and T2D risk (odds ratio = 0.95, p = 2.5 × 10-3). While we found no evidence of causal associations between TSH or fT4 levels and obesity traits, we found that a one SD increase in genetically predicted BMI was associated with a 0.075 SD decrease in fT4 levels (p = 3.6 × 10-4). Conclusions: Variation in normal range thyroid function affects serum cholesterol levels, blood pressure, and T2D risk.

Original languageEnglish
Pages (from-to)721-731
Number of pages11
Issue number5
Publication statusPublished - 3 May 2021

Bibliographical note

Funding Information:
This work was supported by the Exchange in Endocrinology Expertise (3E) program of the European Union of Medical Specialists (UEMS), Section and Board of Endocrinology (A.K.). This work was supported by funding from the European and American Thyroid Associations, the Erasmus University Rotterdam, and the Dutch Organization for Scientific Research (NWO) (M.M.). This work was supported by the British Heart Foundation (BHF) grant RG/14/5/ 30893 (P.D.) and forms part of the research themes contributing to the translational research portfolios of the Barts Biomedical Research Centre funded by the UK National Institute for Health Research (NIHR).

Publisher Copyright:
© 2021, Mary Ann Liebert, Inc., publishers.


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