Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into the complex genetic architecture
Authors: Chia Ruth , Sabir Marya S. , Bandres-Ciga Sara , Saez-Atienzar Sara , Reynolds Regina H. , Gustavsson Emil , Walton Ronald L. , Ahmed Sarah , Viollet Coralie , Ding Jinhui , Makarious Mary B. , Diez-Fairen Monica , Portley Makayla K. , Shah Zalak , Abramzon Yevgeniya , Hernandez Dena G. , Blauwendraat Cornelis , Stone David J. , Eicher John , Parkkinen Laura , Ansorge Olaf , Clark Lorraine , Honig Lawrence S. , Marder Karen , Lemstra Afina , George-Hyslop Peter St , Londos Elisabet , Morgan Kevin , Lashley Tammaryn , Warner Thomas T. , Jaunmuktane Zane , Galasko Douglas , Santana Isabel , Tienari Pentti J. , Myllykangas Liisa , Oinas Minna , Cairns Nigel J. , Morris John C. , Halliday Glenda M. , Van Deerlin Vivianna M. , Trojanowski John Q. , Grassano Maurizio , Calvo Andrea , Mora Gabriele , Canosa Antonio , Floris Gianluca , Bohannan Ryan C. , Brett Francesca , Gan-Or Ziv , Geiger Joshua T. , Moore Anni , May Patrick , Krüger Rejko , Goldstein David , Lopez Grisel , Tayebi Nahid , Sidransky Ellen ,   the Fox Investigation for New Discovery of Biomarkers; The American Genome Center; Lucy Norcliffe-Kaufmann, Palma Jose-Alberto , Kaufmann Horacio , Shakkottai Vikram , Perkins Matthew , Newell Kathy L. , Gasser Thomas , Schulte Claudia , Landi Francesco , Salvi Erika , Cusi Daniele , Masliah Eliezer , Kim Ronald C. , Caraway Chad A. , Monuki Ed , Brunetti Maura , Dawson Ted M. , Rosenthal Liana S. , Albert Marilyn S. , Pletnikova Olga , Troncoso Juan C. , Flanagan Margaret E. , Mao Qinwen , Bigio Eileen H. , Rodríguez-Rodríguez Eloy , Infante Jon , Lage Carmen , González-Aramburu Isabel , Sanchez-Juan Pascual , Ghetti Bernardino , Keith Julia , Black Sandra E. , Masellis Mario , Rogaeva Ekaterina , Duyckaerts Charles , Brice Alexis , Lesage Suzanne , Xiromerisiou Georgia , Barrett Matthew J. , Tilley Bension S. , Gentleman Steve , Logroscino Giancarlo , Serrano Geidy E. , Beach Thomas G. , McKeith Ian G. , Thomas Alan J. , Attems Johannes , Morris Christopher M. , Palmer Laura , Love Seth , Troakes Claire , Al-Sarraj Safa , Hodges Angela K. , Aarsland Dag , Klein Gregory , Kaiser Scott M. , Woltjer Randy , Pastor Pau , Bekris Lynn M. , Leverenz James , Besser Lilah M. , Kuzma Amanda , Renton Alan E. , Goate Alison , Bennett David A. , Scherzer Clemens R. , Morris Huw R. , Ferrari Raffaele , Albani Diego , Brown Stuart Pickering- , Faber Kelley , Kukull Walter , Morenas-Rodriguez Estrella , Lleó Alberto , Fortea Juan , Alcolea Daniel , Clarimon Jordi , Nalls Michael A. , Ferrucci Luigi , Resnick Susan M. , Tanaka Toshiko , Foroud Tatiana M. , Graff-Radford Neill R. , Wszolek Zbigniew K. , Ferman Tanis , Boeve Bradley F. , Hardy John A. , Topol Eric , Torkamani Ali , Singleton Andrew B. , Ryten Mina , Dickson Dennis , Chiò Adriano , Ross Owen A. , Gibbs J. Raphael , Dalgard Clifton L. , Traynor Bryan J. , Scholz Sonja W. 
Published: July 2020

AbstractThe 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 geneGBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer’s and Parkinson’s disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.