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000271349 037__ $$aDZNE-2024-01050
000271349 041__ $$aEnglish
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000271349 1001_ $$aWang, Hui$$b0
000271349 245__ $$aWhole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy.
000271349 260__ $$aLondon$$bBiomed Central$$c2024
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000271349 520__ $$aProgressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of aggregated tau proteins in astrocytes, neurons, and oligodendrocytes. Previous genome-wide association studies for PSP were based on genotype array, therefore, were inadequate for the analysis of rare variants as well as larger mutations, such as small insertions/deletions (indels) and structural variants (SVs).In this study, we performed whole genome sequencing (WGS) and conducted association analysis for single nucleotide variants (SNVs), indels, and SVs, in a cohort of 1,718 cases and 2,944 controls of European ancestry. Of the 1,718 PSP individuals, 1,441 were autopsy-confirmed and 277 were clinically diagnosed.Our analysis of common SNVs and indels confirmed known genetic loci at MAPT, MOBP, STX6, SLCO1A2, DUSP10, and SP1, and further uncovered novel signals in APOE, FCHO1/MAP1S, KIF13A, TRIM24, TNXB, and ELOVL1. Notably, in contrast to Alzheimer's disease (AD), we observed the APOE ε2 allele to be the risk allele in PSP. Analysis of rare SNVs and indels identified significant association in ZNF592 and further gene network analysis identified a module of neuronal genes dysregulated in PSP. Moreover, seven common SVs associated with PSP were observed in the H1/H2 haplotype region (17q21.31) and other loci, including IGH, PCMT1, CYP2A13, and SMCP. In the H1/H2 haplotype region, there is a burden of rare deletions and duplications (P = 6.73 × 10-3) in PSP.Through WGS, we significantly enhanced our understanding of the genetic basis of PSP, providing new targets for exploring disease mechanisms and therapeutic interventions.
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000271349 650_7 $$2Other$$aApolipoprotein E (APOE)
000271349 650_7 $$2Other$$aGenome-Wide Association Study (GWAS)
000271349 650_7 $$2Other$$aProgressive Supranuclear Palsy (PSP)
000271349 650_7 $$2Other$$aStructural Variants (SVs)
000271349 650_7 $$2Other$$aWhole-Genome Sequencing (WGS)
000271349 650_2 $$2MeSH$$aHumans
000271349 650_2 $$2MeSH$$aSupranuclear Palsy, Progressive: genetics
000271349 650_2 $$2MeSH$$aGenetic Predisposition to Disease: genetics
000271349 650_2 $$2MeSH$$aWhole Genome Sequencing
000271349 650_2 $$2MeSH$$aMale
000271349 650_2 $$2MeSH$$aGenome-Wide Association Study
000271349 650_2 $$2MeSH$$aFemale
000271349 650_2 $$2MeSH$$aAged
000271349 650_2 $$2MeSH$$aPolymorphism, Single Nucleotide: genetics
000271349 650_2 $$2MeSH$$aMiddle Aged
000271349 650_2 $$2MeSH$$aAged, 80 and over
000271349 7001_ $$aChang, Timothy S$$b1
000271349 7001_ $$aDombroski, Beth A$$b2
000271349 7001_ $$aCheng, Po-Liang$$b3
000271349 7001_ $$aPatil, Vishakha$$b4
000271349 7001_ $$aValiente-Banuet, Leopoldo$$b5
000271349 7001_ $$aFarrell, Kurt$$b6
000271349 7001_ $$aMclean, Catriona$$b7
000271349 7001_ $$aMolina-Porcel, Laura$$b8
000271349 7001_ $$aRajput, Alex$$b9
000271349 7001_ $$aDe Deyn, Peter Paul$$b10
000271349 7001_ $$aLe Bastard, Nathalie$$b11
000271349 7001_ $$aGearing, Marla$$b12
000271349 7001_ $$aKaat, Laura Donker$$b13
000271349 7001_ $$aVan Swieten, John C$$b14
000271349 7001_ $$aDopper, Elise$$b15
000271349 7001_ $$aGhetti, Bernardino F$$b16
000271349 7001_ $$aNewell, Kathy L$$b17
000271349 7001_ $$aTroakes, Claire$$b18
000271349 7001_ $$ade Yébenes, Justo G$$b19
000271349 7001_ $$aRábano-Gutierrez, Alberto$$b20
000271349 7001_ $$aMeller, Tina$$b21
000271349 7001_ $$aOertel, Wolfgang H$$b22
000271349 7001_ $$0P:(DE-2719)2811600$$aRespondek, Gesine$$b23$$udzne
000271349 7001_ $$aStamelou, Maria$$b24
000271349 7001_ $$0P:(DE-2719)2811333$$aArzberger, Thomas$$b25$$udzne
000271349 7001_ $$aRoeber, Sigrun$$b26
000271349 7001_ $$aMüller, Ulrich$$b27
000271349 7001_ $$0P:(DE-HGF)0$$aHopfner, Franziska$$b28
000271349 7001_ $$aPastor, Pau$$b29
000271349 7001_ $$aBrice, Alexis$$b30
000271349 7001_ $$aDurr, Alexandra$$b31
000271349 7001_ $$aLe Ber, Isabelle$$b32
000271349 7001_ $$aBeach, Thomas G$$b33
000271349 7001_ $$aSerrano, Geidy E$$b34
000271349 7001_ $$aHazrati, Lili-Naz$$b35
000271349 7001_ $$aLitvan, Irene$$b36
000271349 7001_ $$aRademakers, Rosa$$b37
000271349 7001_ $$aRoss, Owen A$$b38
000271349 7001_ $$aGalasko, Douglas$$b39
000271349 7001_ $$aBoxer, Adam L$$b40
000271349 7001_ $$aMiller, Bruce L$$b41
000271349 7001_ $$aSeeley, Willian W$$b42
000271349 7001_ $$aVan Deerlin, Vivanna M$$b43
000271349 7001_ $$aLee, Edward B$$b44
000271349 7001_ $$aWhite, Charles L$$b45
000271349 7001_ $$aMorris, Huw$$b46
000271349 7001_ $$ade Silva, Rohan$$b47
000271349 7001_ $$aCrary, John F$$b48
000271349 7001_ $$aGoate, Alison M$$b49
000271349 7001_ $$aFriedman, Jeffrey S$$b50
000271349 7001_ $$aLeung, Yuk Yee$$b51
000271349 7001_ $$aCoppola, Giovanni$$b52
000271349 7001_ $$aNaj, Adam C$$b53
000271349 7001_ $$aWang, Li-San$$b54
000271349 7001_ $$agenetics study group, P. S. P.$$b55$$eCollaboration Author
000271349 7001_ $$aDalgard, Clifton$$b56
000271349 7001_ $$aDickson, Dennis W$$b57
000271349 7001_ $$0P:(DE-2719)2811373$$aHöglinger, Günter U$$b58$$udzne
000271349 7001_ $$aSchellenberg, Gerard D$$b59
000271349 7001_ $$aGeschwind, Daniel H$$b60
000271349 7001_ $$00000-0002-5305-1181$$aLee, Wan-Ping$$b61
000271349 773__ $$0PERI:(DE-600)2244557-2$$a10.1186/s13024-024-00747-3$$gVol. 19, no. 1, p. 61$$n1$$p61$$tMolecular neurodegeneration$$v19$$x1750-1326$$y2024
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