{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:36:58Z","timestamp":1793320618579,"version":"4.5.0"},"reference-count":47,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Regulation of Thyroid"},{"name":"Parathyroid Function and Blood Calcium Homeostasis"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Thyroid function has been associated with metabolic syndrome (MetS) in a number of observational studies but the direction of effects and the exact causal mechanism of this relationship is still unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To examine genetically predicted effects of thyroid function on MetS risk and its components, and vice versa, using large-scale summary genetic association data.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed a two-sample bidirectional Mendelian randomization (MR) study using summary statistics from the most comprehensive genome-wide association studies (GWAS) of thyroid-stimulating hormone (TSH, n = 119 715), free thyroxine (fT4, n = 49 269), MetS (n = 291 107), and components of MetS: waist circumference (n = 462 166), fasting blood glucose (n = 281 416), hypertension (n = 463 010), triglycerides (TG, n = 441 016) and high-density lipoprotein cholesterol (HDL-C, n = 403 943). We chose the multiplicative random effects inverse variance weighted (IVW) method as the main analysis. Sensitivity analysis included weighted median and mode analysis, as well as MR-Egger and Causal Analysis Using Summary Effect estimates (CAUSE).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Our results suggest that higher fT4 levels lower the risk of developing MetS (OR = 0.96, P = .037). Genetically predicted fT4 was also positively associated with HDL-C (\u03b2 = 0.02, P = .008), while genetically predicted TSH was positively associated with TG (\u03b2 = 0.01, P = .044). These effects were consistent across different MR analyses and confirmed with the CAUSE analysis. In the reverse direction MR analysis, genetically predicted HDL-C was negatively associated with TSH (\u03b2 = \u22120.03, P = .046) in the main IVW analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our study suggests that variations in normal-range thyroid function are causally associated with the diagnosis of MetS and with lipid profile, while in the reverse direction, HDL-C has a plausible causal effect on reference-range TSH levels.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgad371","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T18:05:44Z","timestamp":1687197944000},"page":"3190-3200","source":"Crossref","is-referenced-by-count":29,"title":["Thyroid Function and Metabolic Syndrome: A Two-Sample Bidirectional Mendelian Randomization Study"],"prefix":"10.1210","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5672-871X","authenticated-orcid":false,"given":"Nikolina","family":"Plei\u0107","sequence":"first","affiliation":[{"name":"Department of Medical Biology, University of Split, School of Medicine , Split, 21000 \u00a0 Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7056-6443","authenticated-orcid":false,"given":"Ivana","family":"Gunja\u010da","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, University of Split, School of Medicine , Split, 21000 \u00a0 Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4223-4190","authenticated-orcid":false,"given":"Mirjana","family":"Babi\u0107 Leko","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, University of Split, School of Medicine , Split, 21000 \u00a0 Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8120-2891","authenticated-orcid":false,"given":"Tatijana","family":"Zemunik","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, University of Split, School of Medicine , Split, 21000 \u00a0 Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,6,20]]},"reference":[{"issue":"7","key":"2023111712403969600_dgad371-B1","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1210\/er.2008-0024","article-title":"The metabolic syndrome","volume":"29","author":"Cornier","year":"2008","journal-title":"Endocr Rev"},{"issue":"7","key":"2023111712403969600_dgad371-B2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S","article-title":"Definition, diagnosis and classification of diabetes mellitus and its complications. 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