{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T15:59:16Z","timestamp":1776355156516,"version":"3.51.2"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Observational studies suggested celiac disease (CD) possibly be a risk factor for premature ovarian failure (POF). However, causality remains unclear. And hypothyroidism and systemic lupus erythematosus may be the mediating factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed 2\u2010sample Mendelian randomization (2SMR) to infer a causal relationship between CD and POF using genome\u2010wide association study summary data obtained from IEU OpenGWAS database and FinnGen R12 database. Inverse\u2010variance weighted method was used as the main analysis of MR. Heterogeneity was measured based on Cochran's <jats:italic>Q<\/jats:italic> value. We used the Two\u2010Step MR to analyze whether hypothyroidism and SLE are mediators of the causal relationship between CD and POF. Summary level data of the hypothyroidism and SLE were obtained from IEU OpenGWAS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetically predicted CD may increase the risk of POF by 16% (odds ratio [OR]: 1.16, 95% CI: 1.06\u20131.26, <jats:italic>p<\/jats:italic> = 0.001). Hypothyroidism and SLE could mediate 13.46% and 26.36% of the association between CD and POF, respectively (<jats:italic>p<\/jats:italic> = 0.038, <jats:italic>p<\/jats:italic> = 0.025).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study revealed that CD has a positive contribution effect on POF. CD can elevate the risk of POF by 16%. Besides, hypothyroidism and SLE played a partial mediating role in the causal relationship between the two.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.70038","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T08:55:55Z","timestamp":1738054555000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic Mediators of Celiac Disease and Premature Ovarian Failure: Hypothyroidism and Systemic Lupus Erythematosus"],"prefix":"10.1111","volume":"93","author":[{"given":"Yuxi","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihong","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Endocrinology The First People's Hospital of Chenzhou ChenZhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoguo","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6802-4393","authenticated-orcid":false,"given":"Yuanhang","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manna","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohu","family":"Chen","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital of Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunge","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology the Second Affiliated Hospital of Zhengzhou University Zhengzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0597-8388","authenticated-orcid":false,"given":"Chaoyan","family":"Yue","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Hospital of Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9278-2569","authenticated-orcid":false,"given":"Xiaowen","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00794-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/2050640619844125"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2019.07.008"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/13625187.2019.1702638"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052594"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000032500"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8529(03)00043-4"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-015-0026-z"},{"issue":"2","key":"e_1_2_9_10_1","first-page":"54","article-title":"Pathogenesis and Causes of Premature Ovarian Failure: An Update","volume":"5","author":"Ebrahimi M.","year":"2011","journal-title":"International Journal of Fertility and Sterility"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deae213"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2019.101369"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.39.3.382"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.06.013"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.18.1.0291"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)55974-3"},{"key":"e_1_2_9_17_1","first-page":"377","article-title":"Alpha\u20101 and Beta\u20101 Thyroid Hormone Receptors on Human Granulosa Cells","volume":"49","author":"Wakim A. N.","year":"1994","journal-title":"Recent Progress in Hormone Research"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(93)90102-P"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(16)56941-6"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02212931"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.humrep.a135805"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1980.60.1.51"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1621\/nrs.07012"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(00)01589-2"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-40-3-512"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02905041"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJWH.S28034"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203315622824"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203311409272"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.14022"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03343578"},{"issue":"3","key":"e_1_2_9_32_1","first-page":"287","article-title":"Autoimmune Hypothyroidism and Intermittent Ovarian Failure\u2014Case Report","volume":"23","author":"Bartmann A. K.","year":"2019","journal-title":"JBRA Assisted Reproduction"}],"container-title":["American Journal of Reproductive Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aji.70038","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T15:52:35Z","timestamp":1743609155000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aji.70038"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,28]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/aji.70038"],"URL":"https:\/\/doi.org\/10.1111\/aji.70038","archive":["Portico"],"relation":{},"ISSN":["1046-7408","1600-0897"],"issn-type":[{"value":"1046-7408","type":"print"},{"value":"1600-0897","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,28]]},"assertion":[{"value":"2024-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70038"}}