{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T14:16:52Z","timestamp":1783433812701,"version":"3.54.6"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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":["Euro J of Neurology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>UNC13A is a genetic modifier of amyotrophic lateral sclerosis (ALS) in European populations, but its role in Chinese patients remains incompletely characterized. We investigated the spectrum of UNC13A variation and its impact on disease risk and progression in a Chinese ALS cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed an integrated genetic analysis of 1,533 Chinese ALS patients and 1,405 controls, including rare variant burden testing, genome\u2010wide survival analysis, haplotype mapping, and conditional analyses. An integrated clinical\u2010genetic prognostic score was developed and validated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Rare deleterious UNC13A variants were not associated with ALS risk. We identified two independent haplotype blocks with distinct clinical impacts. Block 1 (tagged by rs75421007) was associated with reduced baseline muscle strength (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.030), while Block 2 (tagged by rs78549703), a brain\u2010specific splicing QTL, was the primary driver of survival heterogeneity. The European variant rs12608932 showed a survival association in single\u2010marker analysis (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.024), but conditional analyses revealed its effect was not independent of Block 2. An integrated prognostic score combining clinical factors and Block 2 haplotype stratified patients into low\u2010, intermediate\u2010, and high\u2010risk groups (median survival: 52.6, 37.1, and 32.0\u2009months;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), with decision curve analysis confirming clinical utility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study delineates UNC13A genetic architecture in Chinese ALS, identifying two independent haplotype blocks that differentially influence disease severity and survival. The Block 2 haplotype, which includes a brain sQTL, is a major determinant of survival heterogeneity and may inform patient stratification in future studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70653","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:49:58Z","timestamp":1780321798000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct\n                    <scp>UNC13A<\/scp>\n                    Haplotype Blocks Define Disease Severity and Survival in Chinese Amyotrophic Lateral Sclerosis"],"prefix":"10.1111","volume":"33","author":[{"given":"Cailin","family":"He","sequence":"first","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University, Jiangxi (National Regional Center for Neurological Diseases)  Nanchang Jiangxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University, Jiangxi (National Regional Center for Neurological Diseases)  Nanchang Jiangxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanchun","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University, Jiangxi (National Regional Center for Neurological Diseases)  Nanchang Jiangxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9058-8340","authenticated-orcid":false,"given":"Linxin","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University, Jiangxi (National Regional Center for Neurological Diseases)  Nanchang Jiangxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meirong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University, Jiangxi (National Regional Center for Neurological Diseases)  Nanchang Jiangxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University, Jiangxi (National Regional Center for Neurological Diseases)  Nanchang Jiangxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University, Jiangxi (National Regional Center for Neurological Diseases)  Nanchang Jiangxi P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University, Jiangxi (National Regional Center for Neurological Diseases)  Nanchang Jiangxi P. R. China"},{"name":"National Clinical Research Center for Geriatric Diseases (Xiangya Hospital of Central South University)  Changsha Hunan P. R. China"},{"name":"Key Laboratory of Hunan Province for Neurodegenerative Disorders Central South University  Changsha Hunan P. R. China"},{"name":"Center for Medical Genetics, School of Life Sciences Central South University  Changsha Hunan P. R. China"},{"name":"Engineering Research Center of Hunan Province for Cognitive Impairment Disorders, Central South University  Changsha Hunan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University, Jiangxi (National Regional Center for Neurological Diseases)  Nanchang Jiangxi P. R. China"},{"name":"National Clinical Research Center for Geriatric Diseases (Xiangya Hospital of Central South University)  Changsha Hunan P. R. China"},{"name":"Key Laboratory of Hunan Province for Neurodegenerative Disorders Central South University  Changsha Hunan P. R. China"},{"name":"Center for Medical Genetics, School of Life Sciences Central South University  Changsha Hunan P. R. China"},{"name":"Engineering Research Center of Hunan Province for Cognitive Impairment Disorders, Central South University  Changsha Hunan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanjun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University, Jiangxi (National Regional Center for Neurological Diseases)  Nanchang Jiangxi P. R. China"},{"name":"Jiangxi Provincial People's Hospital, Clinical College of Nanchang Medical College First Affiliated Hospital of Nanchang Medical College  Nanchang Jiangxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University, Jiangxi (National Regional Center for Neurological Diseases)  Nanchang Jiangxi P. R. China"},{"name":"Jiangxi Provincial People's Hospital, Clinical College of Nanchang Medical College First Affiliated Hospital of Nanchang Medical College  Nanchang Jiangxi People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0313-3434","authenticated-orcid":false,"given":"Renshi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University, Jiangxi (National Regional Center for Neurological Diseases)  Nanchang Jiangxi P. R. 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China"},{"name":"Engineering Research Center of Hunan Province for Cognitive Impairment Disorders, Central South University  Changsha Hunan P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2120-1576","authenticated-orcid":false,"given":"Beisha","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University, Jiangxi (National Regional Center for Neurological Diseases)  Nanchang Jiangxi P. R. China"},{"name":"National Clinical Research Center for Geriatric Diseases (Xiangya Hospital of Central South University)  Changsha Hunan P. R. China"},{"name":"Key Laboratory of Hunan Province for Neurodegenerative Disorders Central South University  Changsha Hunan P. R. China"},{"name":"Center for Medical Genetics, School of Life Sciences Central South University  Changsha Hunan P. R. 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