{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:02:17Z","timestamp":1792551737900,"version":"4.5.0"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Hrvatska Zaklada za Znanost","doi-asserted-by":"publisher","award":["2593"],"award-info":[{"award-number":["2593"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Numerous organs, including the thyroid gland, depend on vitamin D to function normally. Insufficient levels of serum 25-hydroxyvitamin D [25(OH)D] are seen as a potential factor contributing to the emergence of several thyroid disorders, however, the causal relationship remains unclear. Here we use a Mendelian randomization (MR) approach to investigate the causal effect of serum 25(OH)D concentration on the indicators of thyroid function.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a two-sample MR analysis utilizing summary data from the most extensive genome-wide association studies (GWAS) of serum 25(OH)D concentration (n = 443,734 and 417,580), thyroid-stimulating hormone (TSH, n = 271,040), free thyroxine (fT4, n = 119,120), free triiodothyronine (fT3, n = 59,061), total triiodothyronine (TT3, n = 15,829), as well as thyroid peroxidase antibody levels and positivity (TPOAb, n = 12,353 and n = 18,297), low TSH (n = 153,241), high TSH (n = 141,549), autoimmune hypothyroidism (n = 287,247) and autoimmune hyperthyroidism (n = 257,552). The primary analysis was conducted using the multiplicative random-effects inverse variance weighted (IVW) method. The weighted mode, weighted median, MR-Egger, MR-PRESSO, and Causal Analysis Using Summary Effect estimates (CAUSE) were used in the sensitivity analysis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The IVW, as well as MR Egger and CAUSE analysis, showed a suggestive causal effect of 25(OH)D concentration on high TSH. Each 1 SD increase in serum 25(OH)D concentration was associated with a 12% decrease in the risk of high TSH (p = 0.02). Additionally, in the MR Egger and CAUSE analysis, we found a suggestive causal effect of 25(OH)D concentration on autoimmune hypothyroidism. Specifically, each 1 SD increase in serum 25(OH)D concentration was associated with a 16.34% decrease in the risk of autoimmune hypothyroidism (p = 0.02).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our results support a suggestive causal effect which was negative in direction across all methods used, meaning that higher genetically predicted vitamin D concentration possibly lowers the odds of having high TSH or autoimmune hypothyroidism. Other thyroid parameters were not causally influenced by vitamin D serum concentration.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0304253","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T17:33:45Z","timestamp":1718904825000},"page":"e0304253","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Vitamin D and thyroid function: A mendelian randomization study"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5672-871X","authenticated-orcid":true,"given":"Nikolina","family":"Plei\u0107","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4223-4190","authenticated-orcid":true,"given":"Mirjana","family":"Babi\u0107 Leko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Gunja\u010da","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8120-2891","authenticated-orcid":true,"given":"Tatijana","family":"Zemunik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,6,20]]},"reference":[{"issue":"1","key":"pone.0304253.ref001","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/1477-7827-9-146","article-title":"Vitamin D\u2014roles in women\u2019s reproductive health?","volume":"9","author":"M Grundmann","year":"2011","journal-title":"Reproductive Biology and Endocrinology"},{"issue":"3","key":"pone.0304253.ref002","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.chembiol.2013.12.016","article-title":"Vitamin D Metabolism, Mechanism of Action, and Clinical Applications.","volume":"21","author":"D. Bikle Daniel","year":"2014","journal-title":"Chemistry & Biology."},{"issue":"2","key":"pone.0304253.ref003","doi-asserted-by":"crossref","first-page":"113","DOI":"10.4103\/0253-7613.77335","article-title":"Vitamin D as a promising anticancer agent.","volume":"43","author":"CK Chakraborti","year":"2011","journal-title":"Indian J Pharmacol."},{"issue":"9","key":"pone.0304253.ref004","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1136\/ard.2007.069831","article-title":"Vitamin D and autoimmunity: new aetiological and therapeutic considerations","volume":"66","author":"A Yoav","year":"2007","journal-title":"ANNALS OF THE RHEUMATIC DISEASES"},{"key":"pone.0304253.ref005","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.mce.2017.06.008","article-title":"Vitamin D endocrinology of bone mineralization","volume":"453","author":"M van Driel","year":"2017","journal-title":"Molecular and Cellular Endocrinology"},{"issue":"3","key":"pone.0304253.ref006","doi-asserted-by":"crossref","first-page":"e58725","DOI":"10.1371\/journal.pone.0058725","article-title":"Influence of Vitamin D Status and Vitamin D3 Supplementation on Genome Wide Expression of White Blood Cells: A Randomized Double-Blind Clinical Trial.","volume":"8","author":"A Hossein-nezhad","year":"2013","journal-title":"PloS one"},{"issue":"15","key":"pone.0304253.ref007","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.2174\/1381612825666190705193227","article-title":"Vitamin D: A Micronutrient Regulating Genes","volume":"25","author":"C. Carlberg","year":"2019","journal-title":"CURRENT PHARMACEUTICAL DESIGN."},{"issue":"4","key":"pone.0304253.ref008","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/S2213-8587(14)70225-6","article-title":"Iodine deficiency and thyroid disorders","volume":"3","author":"MB Zimmermann","year":"2015","journal-title":"The Lancet Diabetes & Endocrinology."},{"key":"pone.0304253.ref009","doi-asserted-by":"crossref","first-page":"1297658","DOI":"10.1155\/2017\/1297658","article-title":"Selenium and Thyroid Disease: From Pathophysiology to Treatment.","volume":"2017","author":"M Ventura","year":"2017","journal-title":"Int J Endocrinol"},{"key":"pone.0304253.ref010","article-title":"Relationship between dietary selenium intake and serum thyroid function measures in U.S. adults: Data from NHANES 2007\u20132012.","volume":"9","author":"F Liu","year":"2022","journal-title":"FRONTIERS IN NUTRITION."},{"issue":"3","key":"pone.0304253.ref011","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/s41574-019-0311-6","article-title":"Selenium in thyroid disorders\u2014essential knowledge for clinicians","volume":"16","author":"KH Winther","year":"2020","journal-title":"Nature Reviews Endocrinology"},{"key":"pone.0304253.ref012","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.nut.2018.04.015","article-title":"Vitamin D deficiency as a risk factor for thyroid cancer: A meta-analysis of case-control studies","volume":"57","author":"J Zhao","year":"2019","journal-title":"Nutrition"},{"issue":"1","key":"pone.0304253.ref013","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/s12902-021-00831-5","article-title":"Vitamin D and thyroid disorders: a systematic review and Meta-analysis of observational studies","volume":"21","author":"S Taheriniya","year":"2021","journal-title":"BMC Endocrine 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