{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T12:13:46Z","timestamp":1785500026297,"version":"3.56.0"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270701"],"award-info":[{"award-number":["32270701"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32470708"],"award-info":[{"award-number":["32470708"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017607","name":"Shenzhen Municipal Fundamental Research Program","doi-asserted-by":"publisher","award":["JCYJ20240813151132042"],"award-info":[{"award-number":["JCYJ20240813151132042"]}],"id":[{"id":"10.13039\/501100017607","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":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Genetic variants on the X chromosome have been linked to susceptibility for Parkinson's disease (PD), but their roles in disease progression remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>This study investigated associations between X chromosome variants and longitudinal cognitive decline or motor impairment in patients with PD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted combined (male + female) and stratified X\u2010chromosome\u2010wide survival studies (XWSS) in 4467 patients with PD\u00a0with 33,406 longitudinal visits. Cognitive decline was defined as global cognitive impairment (GCI, Mini Mental State Exam score\u2009\u226425), whereas motor impairment was evaluated by Hoehn and Yahr stage 3 (HY3). Expression quantitative trait locus (eQTL) and genetic colocalization analyses were systematically performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 40 common variants in the X\u2010chromosome\u2010wide screen associated with longitudinal progression of PD with <jats:italic>P<\/jats:italic>\u2010value &lt;9.27\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup>, including 11 independent loci associated with cognitive decline and two with motor impairment. The rs142724191 and rs144112368 variants were associated with cognitive decline in both combined and male\u2010only analyses. rs111708875 reached genome\u2010wide significance for motor progression in female cases (hazard ratio [HR] =\u20093.98, 95% confidence interval [CI]:\u2009\u20092.54\u20136.25) with <jats:italic>P<\/jats:italic>\u2010value\u2009=\u20091.84\u2009\u00d7\u200910<jats:sup>\u22129<\/jats:sup>. All these variants were independent with X chromosome susceptibility loci associated with PD, Alzheimer's disease, or Lewy body dementia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our XWSS identified novel genetic progression\u2010associated loci on the X chromosome for PD, providing new insights into the X chromosome\u2010linked genetic underpinnings of PD. \u00a9 2025 International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.30252","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T07:18:32Z","timestamp":1748935112000},"page":"1908-1918","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic Analysis of the X Chromosome Associates Loci with Progression of Parkinson's Disease"],"prefix":"10.1002","volume":"40","author":[{"given":"Yu","family":"Liao","sequence":"first","affiliation":[{"name":"Shenzhen Key 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Medicine, Shenzhen Campus of Sun Yat\u2010sen University  Shenzhen Guangdong China"},{"name":"Department of Medical Informatics and Neurobiology Research Center School of Medicine, Shenzhen Campus of Sun Yat\u2010Sen University  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Christophe","family":"Corvol","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau\u2013Paris Brain Institute\u2013ICM, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre National de la Recherche Scientifique, Assistance Publique H\u00f4pitaux de Paris, D\u00e9partement de Neurologie et de G\u00e9n\u00e9tique, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re  Paris 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