{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:56:10Z","timestamp":1780394170347,"version":"3.54.1"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T00:00:00Z","timestamp":1605225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81430023"],"award-info":[{"award-number":["81430023"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Parkinson\u2019s disease (PD) and essential tremor (ET) are the two most common movement disorders. A significant overlap in clinical features, epidemiology, imaging, and pathology suggests that PD and ET may also share common genetic risk factors. Previous studies have only assessed a limited number of ET\u2010associated genes in PD patients and vice versa. Consequently, the genetic association between PD and ET remains incompletely characterized. In this study, we systematically investigated a potential association between rare coding variants in ET\u2010associated genes and PD, in a relatively large Chinese population cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate the genetic association between ET and PD, we performed the sequence kernel association testing (SKAT\u2010O) to explore the variant burden of 33 ET\u2010associated genes, using whole\u2010exome sequencing (WES) data from 1494 early\u2010onset PD (EOPD) patients and 1357 control subjects from mainland China.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report that rare loss\u2010of\u2010function and damaging missense variants of <jats:italic>TNEM4<\/jats:italic> are suggestively associated with EOPD (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.026), damaging missense variants of <jats:italic>TNEM4<\/jats:italic> alone are also suggestively associated with EOPD (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.032). No other rare damaging variants in ET\u2010related genes were significantly associated with EOPD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>This is the first systematic analysis of ET\u2010associated genes in EOPD. The suggestive association between <jats:italic>TNEM4<\/jats:italic> and EOPD provides new evidence for a genetic link between ET and PD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51248","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T09:54:10Z","timestamp":1605261250000},"page":"119-125","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Rare variant analysis of essential tremor\u2010associated genes in early\u2010onset Parkinson\u2019s disease"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4869-6284","authenticated-orcid":false,"given":"Dongxiao","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Neurology Xiangya Hospital Central South University Changsha Hunan 410008 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