{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T03:27:54Z","timestamp":1787110074338,"version":"build-2736575974"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Parkinson's disease (PD) is a progressive neurodegenerative disorder whose aetiology involves an intricate interplay of genetic, immune, metabolic and environmental factors. Endocrine dysfunction\u2014particularly disturbances of thyroid hormone signalling\u2014has been proposed as a contributor to neurodegeneration, but conventional observational studies have produced inconsistent results, and prior Mendelian randomization (MR) work has largely focused on continuous thyroid biomarkers rather than clinically defined hyperthyroid disease states. To clarify this relationship, we performed a two\u2010sample bidirectional and multivariable MR (MVMR) analysis using large\u2010scale genome\u2010wide association study (GWAS) summary statistics from the FinnGen and IEU Open GWAS databases (European ancestry). Single\u2010nucleotide polymorphisms (SNPs) reaching genome\u2010wide significance (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20095\u2009\u00d7\u200910\n                    <jats:sup>\u22128<\/jats:sup>\n                    ) for Graves' disease and thyrotoxicosis with diffuse goitre served as instrumental variables. The inverse\u2010variance weighted (IVW) method was the primary analysis, complemented by MR\u2013Egger, weighted median, weighted mode and simple mode estimators, and MVMR adjusted for smoking, alcohol consumption, and body mass index (BMI). In forward analyses, genetically proxied Graves' disease (OR\u2009=\u20090.942, 95% CI 0.901\u20130.985,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008) and thyrotoxicosis with diffuse goitre (OR\u2009=\u20090.929, 95% CI 0.879\u20130.982,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.009) were associated with a lower risk of PD, whereas reverse analyses showed no significant effect of genetic liability to PD on either thyroid trait. The inverse associations remained stable across MVMR models, and sensitivity analyses (Cochran's\n                    <jats:italic>Q<\/jats:italic>\n                    , MR\u2013Egger intercept, MR\u2010PRESSO, leave\u2010one\u2010out) showed no evidence of heterogeneity or horizontal pleiotropy. Collectively, these findings provide genetic evidence consistent with a protective relationship between hyperthyroid disease states and PD, independent of major lifestyle confounders. By focusing on clinically defined hyperthyroid entities rather than continuous thyroid indices, our study complements prior MR work and highlights the thyroid\u2013brain axis\u2014encompassing thyroid hormone signalling and autoimmune\u2010mediated immune modulation\u2014as a biologically plausible and potentially modifiable contributor to PD risk that warrants further mechanistic and translational investigation.\n                  <\/jats:p>","DOI":"10.1111\/ejn.70616","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T13:12:48Z","timestamp":1783516368000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hyperthyroidism Is Genetically Associated With Reduced Risk of Parkinson's Disease: A Mendelian Randomization Analysis"],"prefix":"10.1111","volume":"64","author":[{"given":"Meng","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Neurology Bazhong Traditional Chinese Medicine Hospital (Bazhou District People's Hospital of Bazhong City)  Bazhong Sichuan Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiren","family":"Huang","sequence":"additional","affiliation":[{"name":"Jiading Branch of Shanghai General Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9149-2159","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Chongqing Sanbo Jiangling Hospital  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2014.10.016"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.31.1.93"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE\u201016\u20100424"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(21)00218\u2010X"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201014156\u20104"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100579\u2010z"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011\u2010008\u20109099\u20100"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(17)30703\u20101"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2020.04.001"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2010.0429"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1305623110"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.3299"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(18)30295\u20103"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010014\u20100201\u20108"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2017.02.010"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(14)61393\u20103"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1377719"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010020\u201002836\u20109"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jbmr\/zjae136"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2014.00082"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168\u20100102(01)00237\u20101"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.13656"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.01103"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201001596\u2010w"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.05.009"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072\u2010023\u201007176\u2010y"}],"container-title":["European 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