Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture
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Chia, Ruth | Sabir, Marya | Bandres-Ciga, Sara | Saez-Atienzar, Sara | Reynolds, Regina | Gustavsson, Emil | Walton, Ronald | Ahmed, Sarah | Viollet, Coralie | Ding, Jinhui | Makarious, Mary | Diez-Fairen, Monica | Portley, Makayla | Shah, Zalak | Abramzon, Yevgeniya | Hernandez, Dena | Blauwendraat, Cornelis | Stone, David | Eicher, John | Parkkinen, Laura | Ansorge, Olaf | Clark, Lorraine | Honig, Lawrence | Marder, Karen | Lemstra, Afina | St George-Hyslop, Peter | Londos, Elisabet | Morgan, Kevin | Lashley, Tammaryn | Warner, Thomas | Jaunmuktane, Zane | Galasko, Douglas | Santana, Isabel | Tienari, Pentti | Myllykangas, Liisa | Oinas, Minna | Cairns, Nigel | Morris, John | Halliday, Glenda | van Deerlin, Vivianna | Trojanowski, John | Grassano, Maurizio | Calvo, Andrea | Mora, Gabriele | Canosa, Antonio | Floris, Gianluca | Bohannan, Ryan | Brett, Francesca | Gan-Or, Ziv | Geiger, Joshua | Moore, Anni | May, Patrick | Krüger, Rejko | Goldstein, David | Lopez, Grisel | Tayebi, Nahid | Sidransky, Ellen | Sotis, Anthony | Sukumar, Gauthaman | Alba, Camille | Lott, Nathaniel | Martinez, Elisa Mcgrath | Tuck, Meila | Singh, Jatinder | Bacikova, Dagmar | Zhang, Xijun | Hupalo, Daniel | Adeleye, Adelani | Wilkerson, Matthew | Pollard, Harvey | Norcliffe-Kaufmann, Lucy | Palma, Jose-Alberto | Kaufmann, Horacio | Shakkottai, Vikram | Perkins, Matthew | Newell, Kathy | Gasser, Thomas | Schulte, Claudia | Landi, Francesco | Salvi, Erika | Cusi, Daniele | Masliah, Eliezer | Kim, Ronald | Caraway, Chad | Monuki, Edwin | Brunetti, Maura | Dawson, Ted | Rosenthal, Liana | Albert, Marilyn | Pletnikova, Olga | Troncoso, Juan | Flanagan, Margaret | Mao, Qinwen | Bigio, Eileen | Rodríguez-Rodríguez, Eloy | Infante, Jon | Lage, Carmen | González-Aramburu, Isabel | Sanchez-Juan, Pascual | Ghetti, Bernardino | Keith, Julia | Black, Sandra | Masellis, Mario | Rogaeva, Ekaterina | Duyckaerts, Charles | Brice, Alexis | Lesage, Suzanne | Xiromerisiou, Georgia | Barrett, Matthew | Tilley, Bension | Gentleman, Steve | Logroscino, Giancarlo | Serrano, Geidy | Beach, Thomas | Mckeith, Ian | Thomas, Alan | Attems, Johannes | Morris, Christopher | Palmer, Laura | Love, Seth | Troakes, Claire | Al-Sarraj, Safa | Hodges, Angela | Aarsland, Dag | Klein, Gregory | Kaiser, Scott | Woltjer, Randy | Pastor, Pau | Bekris, Lynn | Leverenz, James | Besser, Lilah | Kuzma, Amanda | Renton, Alan | Goate, Alison | Bennett, David | Scherzer, Clemens | Morris, Huw | Ferrari, Raffaele | Albani, Diego | Pickering-Brown, Stuart | Faber, Kelley | Kukull, Walter | Morenas-Rodriguez, Estrella | Lleó, Alberto | Fortea, Juan | Alcolea, Daniel | Clarimon, Jordi | Nalls, Mike | Ferrucci, Luigi | Resnick, Susan | Tanaka, Toshiko | Foroud, Tatiana | Graff-Radford, Neill | Wszolek, Zbigniew | Ferman, Tanis | Boeve, Bradley | Hardy, John | Topol, Eric | Torkamani, Ali | Singleton, Andrew | Ryten, Mina | Dickson, Dennis | Chiò, Adriano | Ross, Owen | Gibbs, J. Raphael | Dalgard, Clifton | Traynor, Bryan | Scholz, Sonja
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International audience.
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.
