Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture.
Authors
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 Scholz
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.
