Home > Publications Database > Whole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy. > print

001     271349
005     20240908004653.0
024 7 _ |a 10.1186/s13024-024-00747-3
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037 _ _ |a DZNE-2024-01050
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Wang, Hui
|b 0
245 _ _ |a Whole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy.
260 _ _ |a London
|c 2024
|b Biomed Central
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Progressive 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.
536 _ _ |a 353 - Clinical and Health Care Research (POF4-353)
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588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a Apolipoprotein E (APOE)
|2 Other
650 _ 7 |a Genome-Wide Association Study (GWAS)
|2 Other
650 _ 7 |a Progressive Supranuclear Palsy (PSP)
|2 Other
650 _ 7 |a Structural Variants (SVs)
|2 Other
650 _ 7 |a Whole-Genome Sequencing (WGS)
|2 Other
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Supranuclear Palsy, Progressive: genetics
|2 MeSH
650 _ 2 |a Genetic Predisposition to Disease: genetics
|2 MeSH
650 _ 2 |a Whole Genome Sequencing
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Genome-Wide Association Study
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Polymorphism, Single Nucleotide: genetics
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Aged, 80 and over
|2 MeSH
700 1 _ |a Chang, Timothy S
|b 1
700 1 _ |a Dombroski, Beth A
|b 2
700 1 _ |a Cheng, Po-Liang
|b 3
700 1 _ |a Patil, Vishakha
|b 4
700 1 _ |a Valiente-Banuet, Leopoldo
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700 1 _ |a Farrell, Kurt
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700 1 _ |a Mclean, Catriona
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700 1 _ |a Molina-Porcel, Laura
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700 1 _ |a Rajput, Alex
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700 1 _ |a De Deyn, Peter Paul
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700 1 _ |a Le Bastard, Nathalie
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700 1 _ |a Gearing, Marla
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700 1 _ |a Kaat, Laura Donker
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700 1 _ |a Van Swieten, John C
|b 14
700 1 _ |a Dopper, Elise
|b 15
700 1 _ |a Ghetti, Bernardino F
|b 16
700 1 _ |a Newell, Kathy L
|b 17
700 1 _ |a Troakes, Claire
|b 18
700 1 _ |a de Yébenes, Justo G
|b 19
700 1 _ |a Rábano-Gutierrez, Alberto
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700 1 _ |a Meller, Tina
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700 1 _ |a Oertel, Wolfgang H
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700 1 _ |a Respondek, Gesine
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700 1 _ |a Stamelou, Maria
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700 1 _ |a Arzberger, Thomas
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700 1 _ |a Roeber, Sigrun
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700 1 _ |a Müller, Ulrich
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700 1 _ |a Hopfner, Franziska
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700 1 _ |a Pastor, Pau
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700 1 _ |a Brice, Alexis
|b 30
700 1 _ |a Durr, Alexandra
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700 1 _ |a Le Ber, Isabelle
|b 32
700 1 _ |a Beach, Thomas G
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700 1 _ |a Serrano, Geidy E
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700 1 _ |a Hazrati, Lili-Naz
|b 35
700 1 _ |a Litvan, Irene
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700 1 _ |a Rademakers, Rosa
|b 37
700 1 _ |a Ross, Owen A
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700 1 _ |a Galasko, Douglas
|b 39
700 1 _ |a Boxer, Adam L
|b 40
700 1 _ |a Miller, Bruce L
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700 1 _ |a Seeley, Willian W
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700 1 _ |a Van Deerlin, Vivanna M
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700 1 _ |a Lee, Edward B
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700 1 _ |a White, Charles L
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700 1 _ |a Morris, Huw
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700 1 _ |a de Silva, Rohan
|b 47
700 1 _ |a Crary, John F
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700 1 _ |a Goate, Alison M
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700 1 _ |a Friedman, Jeffrey S
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700 1 _ |a Leung, Yuk Yee
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700 1 _ |a Coppola, Giovanni
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700 1 _ |a Naj, Adam C
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700 1 _ |a Wang, Li-San
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700 1 _ |a genetics study group, P. S. P.
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700 1 _ |a Dalgard, Clifton
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700 1 _ |a Dickson, Dennis W
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700 1 _ |a Höglinger, Günter U
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700 1 _ |a Schellenberg, Gerard D
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700 1 _ |a Geschwind, Daniel H
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700 1 _ |a Lee, Wan-Ping
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773 _ _ |a 10.1186/s13024-024-00747-3
|g Vol. 19, no. 1, p. 61
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