Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture
Ruth Chia,Marya S. Sabir,Sara Bandres-Ciga,Sara Saez-Atienzar,Regina H. Reynolds,Regina H. Reynolds,Regina H. Reynolds,Emil K. Gustavsson,Emil K. Gustavsson,Ronald L. Walton,Samreen Ahmed,Coralie Viollet,Jinhui Ding,Mary B. Makarious,Monica Diez-Fairen,Makayla K. Portley,Zalak Shah,Yevgeniya Abramzon,Yevgeniya Abramzon,Dena G. Hernandez,Cornelis Blauwendraat,David J. Stone,John D. Eicher,Laura Parkkinen,Olaf Ansorge,Lorraine N. Clark,Lawrence S. Honig,Karen Marder,Afina W. Lemstra,Peter St George-Hyslop,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,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,Rejko Krüger,David S. Goldstein,Grisel Lopez,Nahid Tayebi,Ellen Sidransky,Lucy Norcliffe-Kaufmann,Jose-Alberto Palma,Horacio Kaufmann,Vikram G. Shakkottai,Matthew H. 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 Sánchez-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 M. Gentleman,Giancarlo Logroscino,Geidy E. Serrano,Thomas G. Beach,Ian G. McKeith,Alan J. Thomas,Johannes Attems,Christopher Morris,Laura Palmer,Seth Love,Claire Troakes,Safa Al-Sarraj,Angela Hodges,Dag Aarsland,Dag Aarsland,Gregory Klein,Scott M. Kaiser,Randy Woltjer,Pau Pastor,Lynn M. Bekris,James B. Leverenz,Lilah M. Besser,Amanda B. 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-Rodríguez,Estrella Morenas-Rodríguez,Alberto Lleó,Juan Fortea,Daniel Alcolea,Jordi Clarimón,Mike A. Nalls,Luigi Ferrucci,Susan M. Resnick,Toshiko Tanaka,Tatiana Foroud,Neill R. Graff-Radford,Zbigniew K. Wszolek,Tanis J. Ferman,Bradley F. Boeve,John Hardy,Eric J. Topol,Ali Torkamani,Andrew B. Singleton,Mina Ryten,Mina Ryten,Dennis W. Dickson,Adriano Chiò,Owen A. Ross,J. Raphael Gibbs,Clifton L. Dalgard,Bryan J. Traynor,Bryan J. Traynor,Bryan J. Traynor,Sonja W. Scholz +166 more
TLDR
This article performed whole-genome sequencing in large cohorts of Lewy body dementia (LBD) cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community.Abstract:
The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.read more
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