{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T04:51:00Z","timestamp":1789275060375,"version":"build-2803163510"},"reference-count":53,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Previous Mendelian randomization (MR) studies showed an association between hypothyroidism and cataract and between high-normal free thyroxine (FT4) and late age-related macular degeneration (AMD), but not between FT4, thyroid stimulating hormone (TSH), or hyperthyroidism and diabetic retinopathy or cataract. These studies included a limited number of genetic variants for thyroid function and did not investigate autoimmune thyroid disease (AITD) or glaucoma, include bidirectional and multivariable MR (MVMR), and examine sex differences or potential mediation effects of diabetes. We aimed to address this knowledge gap.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We examined the causality and directionality of the associations of AITD, and FT4 and TSH within the reference range with common age-related eye diseases (diabetic retinopathy, cataract, early and late AMD, and primary open-angle glaucoma). We conducted a bidirectional two-sample MR study utilizing publicly available genome-wide association study (GWAS) summary statistics from international consortia (ThyroidOmics, International AMD Genetics Consortium, deCODE, UK Biobank, FinnGen, and DIAGRAM). Bidirectional MR tested directionality, whereas MVMR estimated independent causal effects. Furthermore, we investigated type 1 diabetes (T1D) and type 2 diabetes (T2D) as potential mediators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Genetic predisposition to AITD was associated with increased risk of diabetic retinopathy (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 3 \u00d7 10\n                      <jats:sup>\u22124<\/jats:sup>\n                      ), cataract (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 3 \u00d7 10\n                      <jats:sup>\u22123<\/jats:sup>\n                      ), and T1D (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 1 \u00d7 10\n                      <jats:sup>\u22123<\/jats:sup>\n                      ), but less likely T2D (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.01). MVMR showed attenuated estimates for diabetic retinopathy and cataract when adjusting for T1D, but not T2D. We found pairwise bidirectional associations between AITD, T1D, and diabetic retinopathy. Genetic predisposition to both T1D and T2D increased the risk of diabetic retinopathy and cataract (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 4 \u00d7 10\n                      <jats:sup>\u22124<\/jats:sup>\n                      ). Moreover, genetically predicted higher FT4 within the reference range was associated with an increased risk of late AMD (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.01), particularly in women (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 7 \u00d7 10\n                      <jats:sup>\u22123<\/jats:sup>\n                      ). However, we neither found any association between FT4 and early AMD nor between TSH and early and late AMD. No other associations were observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Genetic predisposition to AITD is associated with risk of diabetic retinopathy and cataract, mostly mediated through increased T1D risk. Reciprocal associations between AITD, diabetic retinopathy, and T1D imply a shared autoimmune origin. The role of FT4 in AMD and potential sex discrepancies needs further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2024.0257","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T13:27:44Z","timestamp":1726493264000},"page":"1414-1423","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["Thyroid Function, Diabetes, and Common Age-Related Eye Diseases: A Mendelian Randomization Study"],"prefix":"10.1177","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3088-4375","authenticated-orcid":false,"given":"Christina","family":"Ellervik","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark."},{"name":"Department of Pathology, Harvard Medical School, Boston, MA, USA."},{"name":"Department of Laboratory Medicine, Boston Children\u2019s Hospital, Boston, MA, USA."},{"name":"Department of Clinical Biochemistry, Zealand University Hospital, K\u00f8ge, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0243-8607","authenticated-orcid":false,"given":"Lena","family":"Boulakh","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Rigshospitalet-Glostrup, Glostrup, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8309-094X","authenticated-orcid":false,"given":"Alexander","family":"Teumer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany."},{"name":"DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6179-1609","authenticated-orcid":false,"given":"Eirini","family":"Marouli","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksander","family":"Ku\u015b","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Buch Hesgaard","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology, Gothenburg University, Sweden."},{"name":"Department of Ophthalmology, Sahlgrenska University Hospital, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Heegaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark."},{"name":"Department of Ophthalmology, Rigshospitalet-Glostrup, Glostrup, Denmark."},{"name":"Department of Pathology, Rigshospitalet-Glostrup, Glostrup, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizette","family":"Blankers","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalie","family":"Sterenborg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3837-2101","authenticated-orcid":false,"given":"Bj\u00f8rn Olav","family":"\u00c5svold","sequence":"additional","affiliation":[{"name":"HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway."},{"name":"Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Wolfgang","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Medici","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3899-1324","authenticated-orcid":false,"given":"Alisa Devedzic","family":"Kjaergaard","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The International AMD Genomics Consortium, and The Mendelian Randomization Study Group for the ThyroidOmics Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(17)30393-5"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(20)30489-7"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2021.101279"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2436-0"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2022.1002"},{"key":"e_1_3_7_7_2","volume-title":"Acta Ophthalmol","author":"Boulakh L","year":"2024","unstructured":"Boulakh L, , Isaksen JL, , Poulsen HE, et al. Thyroid dysfunction and exudative age-related macular degeneration\u2014A Longitudinal Nationwide Registry-Based Cohort Study. Acta Ophthalmol, 2024; in press."},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-015-0329-0"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2010.195032"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/aos.13412"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0192311"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddac052"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00457-9"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2013.131"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1254793"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2022.01.026"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1126339"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06356-1"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-44701-9"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr036"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104992"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05473-8"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-020-00760-7"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3448"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20851-4"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0194321"},{"key":"e_1_3_7_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00931-x"},{"key":"e_1_3_7_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0241-6"},{"key":"e_1_3_7_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03552-w"},{"key":"e_1_3_7_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007081"},{"key":"e_1_3_7_31_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"e_1_3_7_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx034"},{"key":"e_1_3_7_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0631-4"},{"key":"e_1_3_7_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40471-017-0128-6"},{"key":"e_1_3_7_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.6522"},{"key":"e_1_3_7_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0222362"},{"key":"e_1_3_7_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965"},{"key":"e_1_3_7_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyw220"},{"key":"e_1_3_7_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwu283"},{"key":"e_1_3_7_40_2","doi-asserted-by":"publisher","DOI":"10.1268\/8\/wellcomeopenres.15555.3"},{"key":"e_1_3_7_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-018-0424-6"},{"key":"e_1_3_7_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-021-01748-0"},{"key":"e_1_3_7_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152168"},{"key":"e_1_3_7_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.13892"},{"key":"e_1_3_7_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/pedi.13316"},{"key":"e_1_3_7_46_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2022.1435"},{"key":"e_1_3_7_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-04515-x"},{"key":"e_1_3_7_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyab175"},{"key":"e_1_3_7_49_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.64.10.19"},{"key":"e_1_3_7_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04691-2"},{"key":"e_1_3_7_51_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600715R"},{"key":"e_1_3_7_52_2","doi-asserted-by":"publisher","DOI":"10.1159\/000515273"},{"key":"e_1_3_7_53_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.63.5.37"},{"key":"e_1_3_7_54_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.118.301479"}],"container-title":["Thyroid\u00ae"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/thy.2024.0257","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2024.0257","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2024.0257","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T07:27:24Z","timestamp":1775460444000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/thy.2024.0257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":53,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1089\/thy.2024.0257"],"URL":"https:\/\/doi.org\/10.1089\/thy.2024.0257","relation":{},"ISSN":["1050-7256","1557-9077"],"issn-type":[{"value":"1050-7256","type":"print"},{"value":"1557-9077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]}}}