{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:02:40Z","timestamp":1789538560499,"version":"build-2803163510"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019978","name":"Shanghai Pudong New Area Health Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019978","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016070","name":"Shanghai Pudong New District Zhoupu Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016070","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ebm-journal.org"],"crossmark-restriction":true},"short-container-title":["Exp. Biol. Med."],"abstract":"<jats:p>\n                    The pathogenesis of Graves\u2019 disease (GD) has not been fully elucidated, and antibody-mediated immune responses following microbial infection may be involved in its development. We conducted a bidirectional two-sample Mendelian randomization analysis using genetic variants associated with GD and 46 antibody-mediated immune-response phenotypes obtained from large-scale genome-wide association studies. In the forward analysis, none of the antibody-mediated immune-response phenotypes was significantly associated with GD risk after Bonferroni or false discovery rate (FDR) correction. Three Epstein\u2013Barr virus antibody phenotypes showed nominal inverse associations with GD under the inverse-variance weighted method, but these findings did not survive multiple-testing correction and showed evidence of heterogeneity, with additional evidence of horizontal pleiotropy for the ZEBRA antibody phenotype. In the reverse analysis, several associations survived multiple-testing correction, although sensitivity analyses indicated heterogeneity or horizontal pleiotropy for the corrected associations except anti-polyomavirus 2 IgG seropositivity. After jointly considering multiple-testing correction and sensitivity analyses, genetic liability to GD was associated with higher anti-polyomavirus 2 IgG seropositivity (OR = 1.156, 95% CI: 1.050\u20131.273; P = 0.003), which remained significant after FDR correction but did not reach the Bonferroni-corrected threshold. Four additional associations\u2014lower cytomegalovirus pp52 and pp150 antibody levels and higher\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    UreA antibody levels and anti-Merkel cell polyomavirus IgG seropositivity\u2014were nominally significant and should be considered hypothesis-generating. Overall, this bidirectional MR study suggests that genetic liability to GD may influence selected humoral immune-response phenotypes. Notably, the association with anti-polyomavirus 2 IgG seropositivity remained significant after FDR correction, while additional suggestive associations were observed for antibody responses related to CMV,\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    , and Merkel cell polyomavirus. These findings provide new genetic insights into the potential relationship between GD and infection-related humoral immunity, while the potential influence of antibody-mediated immune responses on GD risk warrants further investigation.\n                  <\/jats:p>","DOI":"10.3389\/ebm.2026.11238","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:10:16Z","timestamp":1789535416000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The causal relationship between antibody-mediated immune responses to infections and Graves\u2019 disease: a bi-directional Mendelian randomization analysis"],"prefix":"10.3389","volume":"251","author":[{"given":"Xinwei","family":"Zhang","sequence":"first","affiliation":[{"name":"Graduate School, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]},{"name":"Department of Endocrinology and Rheumatology, Shanghai University 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