{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:00:30Z","timestamp":1790078430767,"version":"4.0.1"},"reference-count":13,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012542","name":"Sichuan Provincial Science and Technology Support Program","doi-asserted-by":"publisher","award":["2024NSFSC0617"],"award-info":[{"award-number":["2024NSFSC0617"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Rare loss\u2010of\u2010function (LoF) variants in\n                      <jats:italic>Intersectin\u20101<\/jats:italic>\n                      (\n                      <jats:italic>ITSN1<\/jats:italic>\n                      ) have recently been identified as strong genetic risk factors for Parkinson's disease (PD) in individuals of European ancestry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim was to determine whether this association extends to other populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed whole\u2010exome sequencing data from 2063 unrelated Chinese patients with PD and performed rare\u2010variant burden analyses together with 3298 controls and publicly available East Asian reference datasets. Gene\u2010based association was evaluated using optimized sequence kernel association test (SKAT\u2010O) for rare LoF variants and predicted damaging missense variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three previously unreported frameshift LoF variants were identified in the patients, all of which were absent from controls and classified as likely pathogenic. Gene\u2010based burden analyses demonstrated enrichment of rare deleterious\n                      <jats:italic>ITSN1<\/jats:italic>\n                      variants in patients with PD across multiple control datasets, supporting the contribution of\n                      <jats:italic>ITSN1<\/jats:italic>\n                      to PD susceptibility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings provide the first independent evidence supporting the association between rare\n                      <jats:italic>ITSN1<\/jats:italic>\n                      variants and PD in an East Asian population, extending previous discoveries from European cohorts. The identification of population\u2010specific pathogenic variants further refines the genetic architecture of\n                      <jats:italic>ITSN1<\/jats:italic>\n                      and reinforces its role as a cross\u2010population susceptibility gene for PD. \u00a9 2026 International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70554","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:04:12Z","timestamp":1790075052000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cross\u2010Ethnic Replication of\n                    <i>Intersectin\u20101<\/i>\n                    as a Parkinson's Disease Susceptibility Gene in a Large Chinese Cohort"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3930-332X","authenticated-orcid":false,"given":"Chunyu","family":"Li","sequence":"first","affiliation":[{"name":"Laboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruwei","family":"Ou","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3754-9246","authenticated-orcid":false,"given":"Qianqian","family":"Wei","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5266-8748","authenticated-orcid":false,"given":"Shichan","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Zheng","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8841-7569","authenticated-orcid":false,"given":"Qirui","family":"Jiang","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4839-7866","authenticated-orcid":false,"given":"Yi","family":"Xiao","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodie","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5956-8301","authenticated-orcid":false,"given":"Junyu","family":"Lin","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4290-7404","authenticated-orcid":false,"given":"Xueping","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Song","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory of Neurodegenerative Disorders, Department of Neurology, National Clinical Research Center for Geriatrics, West China Hospital Sichuan University  Chengdu 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Novel Parkinson's Disease Genetic Risk Factors Within and Across European Populations. 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