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  Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling

van Vliet, N. A., Bos, M. M., Thesing, C. S., Chaker, L., Pietzner, M., Houtman, E., et al. (2021). Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling. BMC Med, 19(1), 266. doi:10.1186/s12916-021-02130-1.

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van Vliet, N. A., Author
Bos, M. M., Author
Thesing, C. S., Author
Chaker, L., Author
Pietzner, M., Author
Houtman, E., Author
Neville, M. J., Author
Li-Gao, R., Author
Trompet, S., Author
Mustafa, R., Author
Ahmadizar, F., Author
Beekman, M., Author
Bot, M., Author
Budde, K., Author
Christodoulides, C., Author
Dehghan, A., Author
Delles, C., Author
Elliott, P., Author
Evangelou, M., Author
Gao, H., Author
Ghanbari, M., Authorvan Herwaarden, A. E., AuthorIkram, M. A., AuthorJaeger, M., AuthorJukema, J. W., AuthorKaraman, I., AuthorKarpe, F., AuthorKloppenburg, M., AuthorMeessen, Jmta, AuthorMeulenbelt, I., AuthorMilaneschi, Y., AuthorMooijaart, S. P., AuthorMook-Kanamori, D. O., AuthorNetea, M. G., AuthorNetea-Maier, R. T., AuthorPeeters, R. P., AuthorPenninx, Bwjh, AuthorSattar, N., AuthorSlagboom, P. E.1, Author           Suchiman, H. E. D., AuthorVölzke, H., AuthorWillems van Dijk, K., AuthorNoordam, R., Authorvan Heemst, D., Author more..
1Slagboom – Molecular Epidemiology, External and Associated Groups, Max Planck Institute for Biology of Ageing, Max Planck Society, ou_3394013              


Free keywords: Adult Aged *Cardiovascular Diseases/diagnosis/epidemiology/genetics Female Humans Lipids Male Mendelian Randomization Analysis Middle Aged *Thyrotropin Thyroxine Young Adult *Coronary artery disease *Mendelian randomization *Metabolomics *Thyroid hormones
 Abstract: BACKGROUND: Observational studies suggest interconnections between thyroid status, metabolism, and risk of coronary artery disease (CAD), but causality remains to be proven. The present study aimed to investigate the potential causal relationship between thyroid status and cardiovascular disease and to characterize the metabolomic profile associated with thyroid status. METHODS: Multi-cohort two-sample Mendelian randomization (MR) was performed utilizing genome-wide significant variants as instruments for standardized thyrotropin (TSH) and free thyroxine (fT4) within the reference range. Associations between TSH and fT4 and metabolic profile were investigated in a two-stage manner: associations between TSH and fT4 and the full panel of 161 metabolomic markers were first assessed hypothesis-free, then directional consistency was assessed through Mendelian randomization, another metabolic profile platform, and in individuals with biochemically defined thyroid dysfunction. RESULTS: Circulating TSH was associated with 52/161 metabolomic markers, and fT4 levels were associated with 21/161 metabolomic markers among 9432 euthyroid individuals (median age varied from 23.0 to 75.4 years, 54.5% women). Positive associations between circulating TSH levels and concentrations of very low-density lipoprotein subclasses and components, triglycerides, and triglyceride content of lipoproteins were directionally consistent across the multivariable regression, MR, metabolomic platforms, and for individuals with hypo- and hyperthyroidism. Associations with fT4 levels inversely reflected those observed with TSH. Among 91,810 CAD cases and 656,091 controls of European ancestry, per 1-SD increase of genetically determined TSH concentration risk of CAD increased slightly, but not significantly, with an OR of 1.03 (95% CI 0.99-1.07; p value 0.16), whereas higher genetically determined fT4 levels were not associated with CAD risk (OR 1.00 per SD increase of fT4; 95% CI 0.96-1.04; p value 0.59). CONCLUSIONS: Lower thyroid status leads to an unfavorable lipid profile and a somewhat increased cardiovascular disease risk.


Language(s): eng - English
 Dates: 2021-11-032021-11-03
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: Other: 34727949
DOI: 10.1186/s12916-021-02130-1
ISSN: 1741-7015
 Degree: -



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Title: BMC Med
Source Genre: Journal
Publ. Info: -
Pages: - Volume / Issue: 19 (1) Sequence Number: - Start / End Page: 266 Identifier: -