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@article{van:2021:10.1186/s12916-021-02130-1,
author = {van, Vliet NA and Bos, MM and Thesing, CS and Chaker, L and Pietzner, M and Houtman, E and Neville, MJ and Li-Gao, R and Trompet, S and Mustafa, R and Ahmadizar, F and Beekman, M and Bot, M and Budde, K and Christodoulides, C and Dehghan, A and Delles, C and Elliott, P and Evangelou, M and Gao, H and Ghanbari, M and van, Herwaarden AE and Ikram, MA and Jaeger, M and Jukema, JW and Karaman, I and Karpe, F and Kloppenburg, M and Meessen, JMTA and Meulenbelt, I and Milaneschi, Y and Mooijaart, SP and Mook-Kanamori, DO and Netea, MG and Netea-Maier, RT and Peeters, RP and Penninx, BWJH and Sattar, N and Slagboom, PE and Suchiman, HED and Volzke, H and Willems, van Dijk K and Noordam, R and van, Heemst D},
doi = {10.1186/s12916-021-02130-1},
journal = {BMC Medicine},
pages = {1--13},
title = {Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling},
url = {http://dx.doi.org/10.1186/s12916-021-02130-1},
volume = {19},
year = {2021}
}

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TY  - JOUR
AB  - BackgroundObservational 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.MethodsMulti-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.ResultsCirculating 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;
AU  - van,Vliet NA
AU  - Bos,MM
AU  - Thesing,CS
AU  - Chaker,L
AU  - Pietzner,M
AU  - Houtman,E
AU  - Neville,MJ
AU  - Li-Gao,R
AU  - Trompet,S
AU  - Mustafa,R
AU  - Ahmadizar,F
AU  - Beekman,M
AU  - Bot,M
AU  - Budde,K
AU  - Christodoulides,C
AU  - Dehghan,A
AU  - Delles,C
AU  - Elliott,P
AU  - Evangelou,M
AU  - Gao,H
AU  - Ghanbari,M
AU  - van,Herwaarden AE
AU  - Ikram,MA
AU  - Jaeger,M
AU  - Jukema,JW
AU  - Karaman,I
AU  - Karpe,F
AU  - Kloppenburg,M
AU  - Meessen,JMTA
AU  - Meulenbelt,I
AU  - Milaneschi,Y
AU  - Mooijaart,SP
AU  - Mook-Kanamori,DO
AU  - Netea,MG
AU  - Netea-Maier,RT
AU  - Peeters,RP
AU  - Penninx,BWJH
AU  - Sattar,N
AU  - Slagboom,PE
AU  - Suchiman,HED
AU  - Volzke,H
AU  - Willems,van Dijk K
AU  - Noordam,R
AU  - van,Heemst D
DO  - 10.1186/s12916-021-02130-1
EP  - 13
PY  - 2021///
SN  - 1741-7015
SP  - 1
TI  - Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling
T2  - BMC Medicine
UR  - http://dx.doi.org/10.1186/s12916-021-02130-1
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000714028800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-02130-1
UR  - http://hdl.handle.net/10044/1/92980
VL  - 19
ER  -

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