Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling
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 dis...
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2021
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oai:doaj.org-article:1f2243259d1f400b993b2f23e8c266e02021-11-08T10:45:52ZHigher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling10.1186/s12916-021-02130-11741-7015https://doaj.org/article/1f2243259d1f400b993b2f23e8c266e02021-11-01T00:00:00Zhttps://doi.org/10.1186/s12916-021-02130-1https://doaj.org/toc/1741-7015Abstract 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.Nicolien A. van VlietMaxime M. BosCarisha S. ThesingLayal ChakerMaik PietznerEvelyn HoutmanMatt J. NevilleRuifang Li-GaoStella TrompetRima MustafaFariba AhmadizarMarian BeekmanMariska BotKathrin BuddeConstantinos ChristodoulidesAbbas DehghanChristian DellesPaul ElliottMarina EvangelouHe GaoMohsen GhanbariAntonius E. van HerwaardenM. Arfan IkramMartin JaegerJ. Wouter JukemaIbrahim KaramanFredrik KarpeMargreet KloppenburgJennifer M. T. A. MeessenIngrid MeulenbeltYuri MilaneschiSimon P. MooijaartDennis O. Mook-KanamoriMihai G. NeteaRomana T. Netea-MaierRobin P. PeetersBrenda W. J. H. PenninxNaveed SattarP. Eline SlagboomH. Eka D. SuchimanHenry VölzkeKo Willems van DijkRaymond NoordamDiana van HeemstBBMRI Metabolomics ConsortiumBMCarticleThyroid hormonesCoronary artery diseaseMetabolomicsMendelian randomizationMedicineRENBMC Medicine, Vol 19, Iss 1, Pp 1-13 (2021) |
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Thyroid hormones Coronary artery disease Metabolomics Mendelian randomization Medicine R |
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Thyroid hormones Coronary artery disease Metabolomics Mendelian randomization Medicine R Nicolien A. van Vliet Maxime M. Bos Carisha S. Thesing Layal Chaker Maik Pietzner Evelyn Houtman Matt J. Neville Ruifang Li-Gao Stella Trompet Rima Mustafa Fariba Ahmadizar Marian Beekman Mariska Bot Kathrin Budde Constantinos Christodoulides Abbas Dehghan Christian Delles Paul Elliott Marina Evangelou He Gao Mohsen Ghanbari Antonius E. van Herwaarden M. Arfan Ikram Martin Jaeger J. Wouter Jukema Ibrahim Karaman Fredrik Karpe Margreet Kloppenburg Jennifer M. T. A. Meessen Ingrid Meulenbelt Yuri Milaneschi Simon P. Mooijaart Dennis O. Mook-Kanamori Mihai G. Netea Romana T. Netea-Maier Robin P. Peeters Brenda W. J. H. Penninx Naveed Sattar P. Eline Slagboom H. Eka D. Suchiman Henry Völzke Ko Willems van Dijk Raymond Noordam Diana van Heemst BBMRI Metabolomics Consortium Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling |
| description |
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. |
| format |
article |
| author |
Nicolien A. van Vliet Maxime M. Bos Carisha S. Thesing Layal Chaker Maik Pietzner Evelyn Houtman Matt J. Neville Ruifang Li-Gao Stella Trompet Rima Mustafa Fariba Ahmadizar Marian Beekman Mariska Bot Kathrin Budde Constantinos Christodoulides Abbas Dehghan Christian Delles Paul Elliott Marina Evangelou He Gao Mohsen Ghanbari Antonius E. van Herwaarden M. Arfan Ikram Martin Jaeger J. Wouter Jukema Ibrahim Karaman Fredrik Karpe Margreet Kloppenburg Jennifer M. T. A. Meessen Ingrid Meulenbelt Yuri Milaneschi Simon P. Mooijaart Dennis O. Mook-Kanamori Mihai G. Netea Romana T. Netea-Maier Robin P. Peeters Brenda W. J. H. Penninx Naveed Sattar P. Eline Slagboom H. Eka D. Suchiman Henry Völzke Ko Willems van Dijk Raymond Noordam Diana van Heemst BBMRI Metabolomics Consortium |
| author_facet |
Nicolien A. van Vliet Maxime M. Bos Carisha S. Thesing Layal Chaker Maik Pietzner Evelyn Houtman Matt J. Neville Ruifang Li-Gao Stella Trompet Rima Mustafa Fariba Ahmadizar Marian Beekman Mariska Bot Kathrin Budde Constantinos Christodoulides Abbas Dehghan Christian Delles Paul Elliott Marina Evangelou He Gao Mohsen Ghanbari Antonius E. van Herwaarden M. Arfan Ikram Martin Jaeger J. Wouter Jukema Ibrahim Karaman Fredrik Karpe Margreet Kloppenburg Jennifer M. T. A. Meessen Ingrid Meulenbelt Yuri Milaneschi Simon P. Mooijaart Dennis O. Mook-Kanamori Mihai G. Netea Romana T. Netea-Maier Robin P. Peeters Brenda W. J. H. Penninx Naveed Sattar P. Eline Slagboom H. Eka D. Suchiman Henry Völzke Ko Willems van Dijk Raymond Noordam Diana van Heemst BBMRI Metabolomics Consortium |
| author_sort |
Nicolien A. van Vliet |
| title |
Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling |
| title_short |
Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling |
| title_full |
Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling |
| title_fullStr |
Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling |
| title_full_unstemmed |
Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling |
| title_sort |
higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort mendelian randomization and metabolomic profiling |
| publisher |
BMC |
| publishDate |
2021 |
| url |
https://doaj.org/article/1f2243259d1f400b993b2f23e8c266e0 |
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