{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T12:45:18Z","timestamp":1782564318888,"version":"3.54.5"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:00:00Z","timestamp":1782518400000},"content-version":"vor","delay-in-days":177,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012175","name":"Zhejiang Traditional Chinese Medicine Administration","doi-asserted-by":"publisher","award":["GZY-ZJ-KJ-24013"],"award-info":[{"award-number":["GZY-ZJ-KJ-24013"]}],"id":[{"id":"10.13039\/501100012175","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006190","name":"Research and Development","doi-asserted-by":"publisher","award":["2025C02199"],"award-info":[{"award-number":["2025C02199"]}],"id":[{"id":"10.13039\/100006190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Endocrinology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Thyroid dysfunction has been linked to hematologic abnormalities, but whether thyroid function has a causal role in myeloproliferative diseases (MDs), including chronic myeloproliferative disease (CMD), remains unclear. We used Mendelian randomization (MR) to assess the potential causal effects of thyroid\u2010related traits on MD risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A two\u2010sample MR analysis was performed using genome\u2010wide association study (GWAS) summary statistics. Outcome data for CMD and MD, excluding chronic myelogenous leukemia (CML), were obtained from the Finnish R12 cohort (European ancestry). Genetic instruments for thyroid traits\u2014including thyrotropin (TSH), free thyroxine (FT4), free\/total triiodothyronine (FT3\/TT3), FT3\/FT4 and TT3\/FT4 ratios, high\/low TSH, and genetic liability to hyperthyroidism and hypothyroidism\u2014were selected at genome\u2010wide significance (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20095\u2009\u00d7\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      ), clumped for linkage disequilibrium (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009&lt;\u20090.001, 10,000\u2009kb), and required F\u2010statistics &gt; 10. Primary causal estimates were obtained using inverse\u2010variance weighted (IVW) MR, with sensitivity analyses using MR\u2010Egger, weighted median, weighted mode, MR\u2010PRESSO, heterogeneity tests, and leave\u2010one\u2010out analyses. Steiger tests were applied to assess directionality, and false discovery rate (FDR) correction was used for multiple comparisons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Most thyroid function measures (TSH, FT4, FT3, TT3, hormone ratios, and hypothyroidism) showed no evidence of a causal association with CMD or MD excluding CML (IVW\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05). A nominal association was observed between self\u2010reported hyperthyroidism\/thyrotoxicosis and CMD, but the effect estimate was implausibly extreme (IVW OR\u2009=\u20095.53\u2009\u00d7\u200910\n                      <jats:sup>\u221214<\/jats:sup>\n                      , 95% CI: 7.78\u2009\u00d7\u200910\n                      <jats:sup>\u221227<\/jats:sup>\n                      \u20130.3935,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0432) and did not remain significant after FDR correction. After outlier removal, genetically predicted hyperthyroidism was nominally associated with MD excluding CML (OR\u2009=\u20090.8806, 95% CI: 0.7954\u20130.9750;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0144), but this also did not survive FDR correction (FDR\u2009=\u20090.2015). Sensitivity analyses and pleiotropy tests did not indicate strong directional pleiotropy for the nominal signals, and Steiger tests supported the hypothesized exposure\u2010to\u2010outcome direction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this MR study, we found no robust evidence for a causal association between most genetically predicted thyroid function traits and MD after multiple\u2010testing correction. The nominal signals observed for hyperthyroidism were phenotype\u2010dependent and statistically unstable, particularly for self\u2010reported CMD. These results emphasize that previously observed associations may be driven by nongenetic factors or clinical confounding.<\/jats:p>\n                    <jats:p>Jingjing Xiang and Jun Yan were co\u2010first authors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ije\/6688740","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T11:47:22Z","timestamp":1782560842000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Causal Association Between Thyroid Function and Myeloproliferative Disease: A Two\u2010Sample Mendelian Randomization Study"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9386-4016","authenticated-orcid":false,"given":"Jingjing","family":"Xiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9957-6578","authenticated-orcid":false,"given":"Jun","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7027-7369","authenticated-orcid":false,"given":"Jianping","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6522-9232","authenticated-orcid":false,"given":"Mengke","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8419-7115","authenticated-orcid":false,"given":"Zhiyin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8353-6705","authenticated-orcid":false,"given":"Shu","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,27]]},"reference":[{"key":"e_1_2_15_1_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12071810"},{"key":"e_1_2_15_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13225666"},{"key":"e_1_2_15_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/ppo.0000000000000013"},{"key":"e_1_2_15_4_2","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.13-2-188"},{"key":"e_1_2_15_5_2","first-page":"165","article-title":"Genetics of Thyroid Function and Disease","volume":"32","author":"Panicker V.","year":"2011","journal-title":"Clinical Biochemist Reviews"},{"key":"e_1_2_15_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14194913"},{"key":"e_1_2_15_7_2","doi-asserted-by":"publisher","DOI":"10.1590\/2359-3997000000044"},{"key":"e_1_2_15_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12288-021-01460-7"},{"key":"e_1_2_15_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43586-021-00092-5"},{"key":"e_1_2_15_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-024-12301-x"},{"key":"e_1_2_15_11_2","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.n2233","volume-title":"Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomisation (STROBE-MR): Explanation and Elaboration","author":"Skrivankova V. 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