{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T16:16:23Z","timestamp":1786637783487,"version":"build-2736575974"},"reference-count":13,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T00:00:00Z","timestamp":1763164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T00:00:00Z","timestamp":1763164800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100032611","name":"Galen and Hilary Weston Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100032611","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["199393"],"award-info":[{"award-number":["199393"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2026,3]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n GBA1<\/jats:italic>\n variants cause Gaucher's disease (GD) in biallelic forms and increase Parkinson's disease (PD) risk in heterozygous carriers. Carriers of mild or severe variants (causing GD type 1 or types 2\u20133) can enroll in clinical trials, whereas those with\n GBA1<\/jats:italic>\n variants classified as unknown are typically excluded.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n We assessed the contribution of unknown variants to PD risk and their relevance for trial stratification.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We meta\u2010analyzed 34 case\u2013control studies (24,060 PD cases, 14,465 controls). Odds ratios (ORs) were estimated using random\u2010effects models and stratified by the American College of Medical Genetics and Genomics (ACMG) criteria.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Unknown variants also classified as variants of uncertain significance (VUSs) per ACMG criteria were associated with PD (OR\u2009=\u20091.59, 95% confidence interval [CI]: 1.25\u20132.02;\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u20090%). VUSs\u2009+\u2009likely pathogenic + pathogenic also showed an association (OR\u2009=\u20091.63, 95% CI: 1.28\u20132.06;\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u20090%).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Unknown\n GBA1<\/jats:italic>\n variants may be considered provisionally in clinical trials if also classified as VUS, likely pathogenic, or pathogenic per ACMG criteria. \u00a9 2025 The Author(s).\n Movement Disorders<\/jats:italic>\n published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mds.70127","type":"journal-article","created":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T11:11:43Z","timestamp":1763205103000},"page":"761-766","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["\n GBA1<\/i>\n <\/scp>\n Variants with Unknown Classification Are Modest Contributors to Parkinson's Disease Susceptibility"],"prefix":"10.1002","volume":"41","author":[{"given":"Sitki Cem","family":"Parlar","sequence":"first","affiliation":[{"name":"Department of Human Genetics McGill University Montr\u00e9al Qu\u00e9bec Canada"},{"name":"The Neuro (Montreal Neurological Institute\u2010Hospital), McGill University Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Department of Neurology and Neurosurgery McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoomin","family":"Lee","sequence":"additional","affiliation":[{"name":"The Neuro (Montreal Neurological Institute\u2010Hospital), McGill University Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Department of Neurology and Neurosurgery McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0332-234X","authenticated-orcid":false,"given":"Ziv","family":"Gan\u2010Or","sequence":"additional","affiliation":[{"name":"Department of Human Genetics McGill University Montr\u00e9al Qu\u00e9bec Canada"},{"name":"The Neuro (Montreal Neurological Institute\u2010Hospital), McGill University Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Department of Neurology and Neurosurgery McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108822"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29314"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1048084"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000104"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001315"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24777"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.30141"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2018.05.009"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1109\/MCSE.2007.55"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00283-1"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.14802\/jmd.23023"},{"key":"e_1_2_9_14_1","unstructured":"TayebiN LichtenbergJ HertzE SidranskyE.Is Gauchian genotyping of GBA1 variants reliable? medRxiv 2023."}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70127","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.70127","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T15:17:28Z","timestamp":1786634248000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.70127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,15]]},"references-count":13,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/mds.70127"],"URL":"https:\/\/doi.org\/10.1002\/mds.70127","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,15]]},"assertion":[{"value":"2025-09-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}