000278787 001__ 278787 000278787 005__ 20260105131136.0 000278787 0247_ $$2pmc$$apmc:PMC12089919 000278787 0247_ $$2doi$$a10.1002/mds.30150 000278787 0247_ $$2pmid$$apmid:40055946 000278787 0247_ $$2ISSN$$a0885-3185 000278787 0247_ $$2ISSN$$a1531-8257 000278787 037__ $$aDZNE-2025-00623 000278787 041__ $$aEnglish 000278787 082__ $$a610 000278787 1001_ $$00000-0003-4043-5060$$aWang, Hui$$b0 000278787 245__ $$aCopy Number Variation and Haplotype Analysis of 17q21.31 Reveals Increased Risk Associated with Progressive Supranuclear Palsy and Gene Expression Changes in Neuronal Cells. 000278787 260__ $$aNew York, NY$$bWiley$$c2025 000278787 3367_ $$2DRIVER$$aarticle 000278787 3367_ $$2DataCite$$aOutput Types/Journal article 000278787 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1748938510_19908 000278787 3367_ $$2BibTeX$$aARTICLE 000278787 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000278787 3367_ $$00$$2EndNote$$aJournal Article 000278787 520__ $$aThe 17q21.31 region with various structural forms characterized by the H1/H2 haplotypes and three large copy number variations (CNVs) represents the strongest risk locus in progressive supranuclear palsy (PSP).To investigate the association between CNVs and structural forms on 17q.21.31 with the risk of PSP.Utilizing whole genome sequencing data from 1684 PSP cases and 2392 controls, the three large CNVs (α, β, and γ) and structural forms within 17q21.31 were identified and analyzed for their association with PSP.We found that the copy number of γ was associated with increased PSP risk (odds ratio [OR] = 1.10, P = 0.0018). From H1β1γ1 (OR = 1.21) and H1β2γ1 (OR = 1.24) to H1β1γ4 (OR = 1.57), structural forms of H1 with additional copies of γ displayed a higher risk for PSP. The frequency of the risk sub-haplotype H1c rises from 1% in individuals with two γ copies to 88% in those with eight copies. Additionally, γ duplication up-regulates expression of ARL17B, LRRC37A/LRRC37A2, and NSFP1, while down-regulating KANSL1. Single-nucleus RNA-seq of the dorsolateral prefrontal cortex analysis reveals γ duplication primarily up-regulates LRRC37A/LRRC37A2 in neuronal cells.The copy number of γ is associated with the risk of PSP after adjusting for H1/H2, indicating that the complex structure at 17q21.31 is an important consideration when evaluating the genetic risk of PSP. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. 000278787 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0 000278787 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000278787 650_7 $$2Other$$a17q21.31 000278787 650_7 $$2Other$$aH1 and H2 haplotypes 000278787 650_7 $$2Other$$acopy number variations 000278787 650_7 $$2Other$$aprogressive supranuclear palsy 000278787 650_7 $$2Other$$asingle‐cell gene expression 000278787 650_2 $$2MeSH$$aHumans 000278787 650_2 $$2MeSH$$aSupranuclear Palsy, Progressive: genetics 000278787 650_2 $$2MeSH$$aDNA Copy Number Variations: genetics 000278787 650_2 $$2MeSH$$aFemale 000278787 650_2 $$2MeSH$$aMale 000278787 650_2 $$2MeSH$$aChromosomes, Human, Pair 17: genetics 000278787 650_2 $$2MeSH$$aAged 000278787 650_2 $$2MeSH$$aHaplotypes: genetics 000278787 650_2 $$2MeSH$$aNeurons: metabolism 000278787 650_2 $$2MeSH$$aGenetic Predisposition to Disease: genetics 000278787 650_2 $$2MeSH$$aMiddle Aged 000278787 650_2 $$2MeSH$$aGene Expression 000278787 7001_ $$00000-0002-9225-9874$$aChang, Timothy S$$b1 000278787 7001_ $$00000-0002-5334-1306$$aDombroski, Beth A$$b2 000278787 7001_ $$00009-0007-0046-0313$$aCheng, Po-Liang$$b3 000278787 7001_ $$00000-0002-9968-9754$$aSi, Ya-Qin$$b4 000278787 7001_ $$00000-0001-5703-7208$$aTucci, Albert$$b5 000278787 7001_ $$aPatil, Vishakha$$b6 000278787 7001_ $$aValiente-Banuet, Leopoldo$$b7 000278787 7001_ $$00000-0003-1949-4074$$aLi, Chong$$b8 000278787 7001_ $$00000-0001-6955-7278$$aFarrell, Kurt$$b9 000278787 7001_ $$00000-0002-0302-5727$$aMclean, Catriona$$b10 000278787 7001_ $$00000-0003-4068-8578$$aMolina-Porcel, Laura$$b11 000278787 7001_ $$00000-0001-9656-318X$$aRajput, Alex$$b12 000278787 7001_ $$00000-0002-2228-2964$$aDe Deyn, Peter Paul$$b13 000278787 7001_ $$00000-0002-7981-2866$$aLe Bastard, Nathalie$$b14 000278787 7001_ 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