{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T18:17:57Z","timestamp":1786817877323,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["MOH\u2010000677"],"award-info":[{"award-number":["MOH\u2010000677"]}],"id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","award":["CNIG23jan\u20100008"],"award-info":[{"award-number":["CNIG23jan\u20100008"]}],"id":[{"id":"10.13039\/501100001349","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":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Transcriptomic changes in the essential tremor (ET)\u2013associated cerebello\u2010thalamo\u2010cortical \u201ctremor network\u201d and their association to brain structure have not been investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim was to characterize molecular changes associated with network\u2010level imaging\u2010derived phenotypes (IDP) found in ET.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed an imaging\u2010transcriptomic study in British adults using imaging\u2010genome\u2010wide association study summary statistics (UK Biobank \u201cBIG40\u201d cohort; n\u2009=\u200933,224, aged 40\u201369\u2009years). We imputed imaging\u2010transcriptomic associations for 184 IDPs and analyzed functional enrichment of gene modules and aggregate network\u2010level phenotypes. Validation was performed in cerebellar\u2010tissue RNA\u2010sequencing data from ET patients and controls (n\u2009=\u200955).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 237,896 individual predicted gene expression levels for 6063 unique genes\/transcripts, we detected 2269 genome\u2010wide significant associations (Bonferroni <jats:italic>P<\/jats:italic>\u2009&lt;\u20092.102e\u20107, 0.95%). These were concentrated in intracellular volume fraction measures of white matter pathways and in genes with putative links to tremor (<jats:italic>MAPT<\/jats:italic>, <jats:italic>ARL17A<\/jats:italic>, <jats:italic>KANSL1<\/jats:italic>, <jats:italic>SPPL2C<\/jats:italic>, <jats:italic>LRRC37A4P<\/jats:italic>, <jats:italic>PLEKHM1<\/jats:italic>, and <jats:italic>FMNL1<\/jats:italic>). Whole\u2010tremor\u2010network cortical thickness was associated with a gene module linked to mitochondrial organization and protein quality control (r\u2009=\u20090.91, <jats:italic>P<\/jats:italic>\u2009=\u20092e\u201070), whereas white\u2010gray T1\u2010weighted magnetic resonance imaging (MRI) contrast in the tremor network was associated with a gene module linked to sphingolipid synthesis and ethanolamine metabolism (r\u2009=\u2009\u22120.90, <jats:italic>P<\/jats:italic>\u2009=\u20092e\u201068). Imputed association effect sizes and RNA\u2010sequencing log\u2010fold change in the validation dataset were significantly correlated for cerebellar peduncular diffusion MRI phenotypes, and there was a close overlap of significant associations between both datasets for gray matter phenotypes (\u03c7<jats:sup>2<\/jats:sup>\u2009=\u20096.40, <jats:italic>P<\/jats:italic>\u2009=\u20090.006).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The identified genes and processes are potential treatment targets for ET, and our results help characterize molecular changes that could in future be used for patient treatment selection or prognosis prediction. \u00a9 2024 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29831","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T23:54:24Z","timestamp":1716249264000},"page":"1119-1130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Association of Gene Expression and Tremor Network Structure"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9503-2093","authenticated-orcid":false,"given":"Thomas","family":"Welton","sequence":"first","affiliation":[{"name":"Department of Research National Neuroscience Institute  Singapore Singapore"},{"name":"Neuroscience and Behavioural Disorders Duke\u2010NUS Medical School  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Chew","sequence":"additional","affiliation":[{"name":"Neuroscience and Behavioural Disorders Duke\u2010NUS Medical School  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7644-5538","authenticated-orcid":false,"given":"Aaron Shengting","family":"Mai","sequence":"additional","affiliation":[{"name":"Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing Han","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Neurology Singapore General Hospital  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling Ling","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Research National Neuroscience Institute  Singapore Singapore"},{"name":"Neuroscience and Behavioural Disorders Duke\u2010NUS Medical School  Singapore Singapore"},{"name":"Department of Diagnostic Radiology Singapore General Hospital  Singapore 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