259cafe7bc4d9b983b69e587d42e014f pmc_33589841.pdf b53e2a9df0bc06a5c498b4041223de9ce29b8b72 pmc_33589841.pdf 9a0e5c169f7234e9d305dbbd3517cd21175dc239dffeeae5f8fa2bc29369e5fe pmc_33589841.pdf Title: Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture Author: Ruth Chia, Marya S. Sabir, Sara Bandres-Ciga, Sara Saez-Atienzar, Regina H. Reynolds, Emil Gustavsson, Ronald L. Walton, Sarah Ahmed, Coralie Viollet, Jinhui Ding, Mary B. Makarious, Monica Diez-Fairen, Makayla K. Portley, Zalak Shah, Yevgeniya Abramzon, Dena G. Hernandez, Cornelis Blauwendraat, David J. Stone, John Eicher, Laura Parkkinen, Olaf Ansorge, Lorraine Clark, Lawrence S. Honig, Karen Marder, Afina Lemstra, Peter St George-Hyslop, Elisabet Londos, Kevin Morgan, Tammaryn Lashley, Thomas T. Warner, Zane Jaunmuktane, Douglas Galasko, Isabel Santana, Pentti J. Tienari, Liisa Myllykangas, Minna Oinas, Nigel J. Cairns, John C. Morris, Glenda M. Halliday, Vivianna M. Van Deerlin, John Q. Trojanowski, Maurizio Grassano, Andrea Calvo, Gabriele Mora, Antonio Canosa, Gianluca Floris, Ryan C. Bohannan, Francesca Brett, Ziv Gan-Or, Joshua T. Geiger, Anni Moore, Patrick May, Rejko Krüger, David S. Goldstein, Grisel Lopez, Nahid Tayebi, Ellen Sidransky, , Lucy Norcliffe-Kaufmann, Jose-Alberto Palma, Horacio Kaufmann, Vikram G. Shakkottai, Matthew Perkins, Kathy L. Newell, Thomas Gasser, Claudia Schulte, Francesco Landi, Erika Salvi, Daniele Cusi, Eliezer Masliah, Ronald C. Kim, Chad A. Caraway, Edwin S. Monuki, Maura Brunetti, Ted M. Dawson, Liana S. Rosenthal, Marilyn S. Albert, Olga Pletnikova, Juan C. Troncoso, Margaret E. Flanagan, Qinwen Mao, Eileen H. Bigio, Eloy Rodríguez-Rodríguez, Jon Infante, Carmen Lage, Isabel González-Aramburu, Pascual Sanchez-Juan, Bernardino Ghetti, Julia Keith, Sandra E. Black, Mario Masellis, Ekaterina Rogaeva, Charles Duyckaerts, Alexis Brice, Suzanne Lesage, Georgia Xiromerisiou, Matthew J. Barrett, Bension S. Tilley, Steve Gentleman, Giancarlo Logroscino, Geidy E. Serrano, Thomas G. Beach, Ian G. McKeith, Alan J. Thomas, Johannes Attems, Christopher M. Morris, Laura Palmer, Seth Love, Claire Troakes, Safa Al-Sarraj, Angela K. Hodges, Dag Aarsland, Gregory Klein, Scott M. Kaiser, Randy Woltjer, Pau Pastor, Lynn M. Bekris, James B. Leverenz, Lilah M. Besser, Amanda Kuzma, Alan E. Renton, Alison Goate, David A. Bennett, Clemens R. Scherzer, Huw R. Morris, Raffaele Ferrari, Diego Albani, Stuart Pickering-Brown, Kelley Faber, Walter A. Kukull, Estrella Morenas-Rodriguez, Alberto Lleó, Juan Fortea, Daniel Alcolea, Jordi Clarimon, Mike A. Nalls, Luigi Ferrucci, Susan M. Resnick, Toshiko Tanaka, Tatiana M. Foroud, Neill R. Graff-Radford, Zbigniew K. Wszolek, Tanis Ferman, Bradley F. Boeve, John A. Hardy, Eric J. Topol, Ali Torkamani, Andrew B. Singleton, Mina Ryten, Dennis W. Dickson, Adriano Chiò, Owen A. Ross, J. Raphael Gibbs, Clifton L. Dalgard, Bryan J. Traynor, Sonja W. ScholzThe American Genome Center Creator: AH XSL Formatter V6.6 MR7 for Linux64 : 6.6.9.39847 (2019-07-29T09:58+09) Producer: Antenna House PDF Output Library 6.6.1477 (Linux64) CreationDate: Thu Mar 11 08:24:42 2021 CET ModDate: Thu Mar 11 08:24:42 2021 CET Custom Metadata: no Metadata Stream: no Tagged: yes UserProperties: no Suspects: no Form: none JavaScript: no Pages: 37 Encrypted: no Page size: 612 x 792 pts (letter) Page rot: 0 File size: 3863160 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- Times-Roman Type 1 Custom no no yes 11 0 Helvetica-Bold Type 1 Custom no no yes 13 0 Helvetica-Oblique Type 1 Standard no no no 15 0 ZVRWIR+Code2000 CID TrueType Identity-H yes yes yes 25 0 Helvetica Type 1 Custom no no yes 30 0 Helvetica-BoldOblique Type 1 Standard no no no 88 0 Times-Bold Type 1 Custom no no yes 474 0 Times-BoldItalic Type 1 Standard no no no 475 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:30:34 CEST RepresentationInformation: pmc_33589841.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:08:55 CEST Size: 3863160 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf Profile: Tagged PDF PDFMetadata: Objects: 0 FreeObjects: 236 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: false CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseOutlines Language: EN Outlines: Item: Title: Abstract Item: Title: Results Children: Item: Title: Genome-wide association analysis identifies new loci associated with LBD. Item: Title: Gene-level aggregation testing identifies GBA as a pleomorphic risk gene. Item: Title: Functional inferences from colocalization and gene expression analyses. Item: Title: LBD risk overlaps with risk profiles of Alzheimer’s disease and Parkinson’s disease. Item: Title: Enrichment analysis identifies pathways involved in LBD. Item: Title: Association of polygenic risk with clinical dementia severity. Item: Title: Discussion Item: Title: Methods Children: Item: Title: Cohort description and study design. Item: Title: Whole-genome sequencing. Item: Title: Sequence alignment, variant calling. Item: Title: Quality control. Item: Title: Statistical analysis for single-variant association. Item: Title: Genotype-pathology association analysis. Item: Title: Colocalization analyses. Item: Title: Cell-type and tissue specificity measures. Item: Title: Heritability analysis. Item: Title: Gene-based rare variant association analysis. Item: Title: Predictions of LBD risk using Alzheimer’s disease and Parkinson’s disease risk scores. Item: Title: Polygenic risk score generation for pathway enrichment and phenotype associations. Item: Title: Data availability. Item: Title: Code availability. Item: Title: Extended Data Item: Title: Extended Data Fig. 1 Item: Title: Extended Data Fig. 2 Item: Title: Extended Data Fig. 3 Item: Title: Extended Data Fig. 4 Item: Title: Extended Data Fig. 5 Item: Title: Extended Data Fig. 6 Item: Title: Extended Data Fig. 7 Item: Title: Extended Data Fig. 8 Item: Title: Extended Data Fig. 9 Item: Title: Extended Data Fig. 10 Item: Title: References Item: Title: References Item: Title: Fig. 1 | Item: Title: Fig. 2 | Item: Title: Fig. 3 | Item: Title: Fig. 4 | Item: Title: Fig. 5 | Item: Title: Table 1 | Filters: FilterPipeline: FlateDecode FilterPipeline: DCTDecode Images: Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 152 ImageHeight: 152 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Image: NisoImageMetadata: FormatName: image/png ImageWidth: 1992 ImageHeight: 2098 BitsPerSample: 8 BitsPerSampleUnit: integer Filter: FlateDecode Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: 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ImageWidth: 1552 ImageHeight: 1689 BitsPerSample: 8 BitsPerSampleUnit: integer Fonts: Type0: Font: BaseFont: ZVRWIR+Code2000 Encoding: Identity-H ToUnicode: true Type1: Font: BaseFont: Helvetica-BoldOblique Font: BaseFont: Times-Bold FirstChar: 32 LastChar: 128 FontDescriptor: FontName: Times-Bold Flags: Nonsymbolic FontBBox: -168, -218, 1000, 935 EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: Times-Roman FirstChar: 32 LastChar: 136 FontDescriptor: FontName: Times-Roman Flags: Nonsymbolic FontBBox: -168, -218, 1000, 898 EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: Times-BoldItalic Font: BaseFont: Helvetica-Bold FirstChar: 32 LastChar: 128 FontDescriptor: FontName: Helvetica-Bold Flags: Nonsymbolic FontBBox: -170, -228, 1003, 962 EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: Helvetica FirstChar: 32 LastChar: 142 FontDescriptor: FontName: Helvetica Flags: Nonsymbolic FontBBox: -166, -225, 1000, 931 EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: Helvetica-Oblique CIDFontType2: Font: BaseFont: ZVRWIR+Code2000 CIDSystemInfo: Registry: Adobe Registry: Identity Supplement: 0 FontDescriptor: FontName: ZVRWIR+Code2000 Flags: Symbolic FontBBox: -1111, -295, 2107, 977 FontFile2: true Pages: Page: Sequence: 1 Page: Sequence: 2 Page: Sequence: 3 Page: Sequence: 4 Page: Sequence: 5 Page: Sequence: 6 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Contents: www.amp-pd.org Rect: 153, 441, 223, 451 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: NCT02014246 Rect: 389, 277, 449, 287 LastModified: D:20210311022442-05'00' Page: Sequence: 8 Annotations: Annotation: Subtype: Link Contents: https://www.genome.gov/27563570/ Rect: 316, 688, 462, 698 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://github.com/gatk-workflows/broad-prod-wgs-germline-snps-indels Rect: 153, 534, 445, 544 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: www.nhlbiwgs.org Rect: 150, 200, 225, 210 LastModified: D:20210311022442-05'00' Page: Sequence: 9 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Contents: https://github.com/RHReynolds/MarkerGenes Rect: 480, 494, 508, 504 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: github.com/RHReynolds/MarkerGenes Rect: 150, 480, 306, 490 LastModified: D:20210311022442-05'00' Page: Sequence: 11 Annotations: Annotation: Subtype: Link Contents: https://www.ebi.ac.uk/gwas/home Rect: 323, 188, 458, 198 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://www.eqtlgen.org/cis-eqtls.html Rect: 231, 174, 385, 184 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: http://resource.psychencode.org/ Rect: 197, 160, 328, 170 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://www.gtexportal.org/home/ Rect: 463, 146, 491, 156 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: www.gtexportal.org/home/ Rect: 150, 132, 257, 142 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: portal.brain-map.org/atlases-and-data/rnaseq/human-mtg/smart-seq Rect: 311, 118, 493, 128 LastModified: D:20210311022442-05'00' Page: Sequence: 12 Annotations: Annotation: Subtype: Link Contents: human-mtg/smart-seq Rect: 150, 720, 237, 730 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://github.com.RHReynolds/MarkerGenes Rect: 261, 706, 445, 716 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://github.com/gatk-workflows/broad-prod-wgs-germline-snps-indels Rect: 153, 620, 445, 630 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://genome.sph.umich.edu/wiki/VerifyBamID Rect: 350, 606, 493, 616 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: VerifyBamID Rect: 150, 592, 204, 602 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://www.cog-genomics.org/plink/2.0/ Rect: 334, 578, 498, 588 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://www.r-project.org Rect: 436, 564, 494, 574 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: project.org Rect: 150, 550, 193, 560 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://github.com/poruloh/Eagle Rect: 181, 508, 313, 518 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://genome.sph.umich.edu/wiki/METAL Rect: 217, 494, 394, 504 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://cnsgenomics.com/software/gcta Rect: 364, 480, 503, 490 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: gcta Rect: 150, 466, 166, 476 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: http://zhanxw.github.io/rvtests/ Rect: 431, 466, 455, 476 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: zhanxw.github.io/rvtests/ Rect: 150, 452, 250, 462 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://doc-openbio.readthedocs.io/projects/annovar/en/latest/ Rect: 153, 438, 399, 448 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://www.cog-genomics.org/plink Rect: 345, 424, 491, 434 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: genome.sph.umich.edu/wiki/LiftOver Rect: 153, 382, 304, 392 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://github.com/chr1swallace/coloc Rect: 291, 368, 443, 378 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://github.com/NathanSkene/EWCE Rect: 418, 340, 493, 350 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: NathanSkene/EWCE Rect: 150, 326, 234, 336 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://www.prsice.info Rect: 153, 312, 247, 322 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://cran.r-project.org/web/packages/gprofiler2/vignettes/gprofiler2.html Rect: 231, 298, 472, 308 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: gprofiler2.html Rect: 150, 284, 210, 294 LastModified: D:20210311022442-05'00' Page: Sequence: 13 Page: Sequence: 14 Page: Sequence: 15 Page: Sequence: 16 Page: Sequence: 17 Page: Sequence: 18 Page: Sequence: 19 Page: Sequence: 20 Page: Sequence: 21 Page: Sequence: 22 Page: Sequence: 23 Page: Sequence: 24 Page: Sequence: 25 Page: Sequence: 26 Page: Sequence: 27 Annotations: Annotation: Subtype: Link Contents: http://biowulf.nih.gov Rect: 466, 563, 485, 571 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: biowulf.nih.gov Rect: 150, 554, 200, 562 LastModified: D:20210311022442-05'00' Annotation: Subtype: Link Contents: https://www.lbda.org/page/what-lbd Rect: 159, 120, 288, 129 LastModified: D:20210311022442-05'00' Page: Sequence: 28 Annotations: Annotation: Subtype: Link Contents: https://www.biorxiv.org/content/10.1101/447367v1 Rect: 255, 387, 440, 396 LastModified: D:20210311022442-05'00' Page: Sequence: 29 Annotations: Annotation: Subtype: Link Contents: https://www.biorxiv.org/content/10.1101/563866v1 Rect: 204, 163, 389, 172 LastModified: D:20210311022442-05'00' Page: Sequence: 30 Page: Sequence: 31 Page: Sequence: 32 Page: Sequence: 33 Page: Sequence: 34 Page: Sequence: 35 Page: Sequence: 36 Page: Sequence: 37 Checksum: ebc2d03a Type: CRC32 Checksum: 259cafe7bc4d9b983b69e587d42e014f Type: MD5 Checksum: b53e2a9df0bc06a5c498b4041223de9ce29b8b72 Type: SHA-1 Checksum: 9a0e5c169f7234e9d305dbbd3517cd21175dc239dffeeae5f8fa2bc29369e5fe Type: SHA-256