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Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its 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
St George-Hyslop, Peter
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 S.
Lopez, Grisel
Tayebi, Nahid
Sidransky, Ellen
Norcliffe-Kaufmann, Lucy
Palma, Jose-Alberto
Kaufmann, Horacio
Shakkottai, Vikram G.
Perkins, Matthew
Newell, Kathy L.
Gasser, Thomas
Schulte, Claudia
Landi, Francesco
Salvi, Erika
Cusi, Daniele
Masliah, Eliezer
Kim, Ronald C.
Caraway, Chad A.
Monuki, Edwin S.
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 B.
Besser, Lilah M.
Kuzma, Amanda
Renton, Alan E.
Goate, Alison
Bennett, David A.
Scherzer, Clemens R.
Morris, Huw R.
Ferrari, Raffaele
Albani, Diego
Pickering-Brown, Stuart
Faber, Kelley
Kukull, Walter A.
Morenas-Rodriguez, Estrella
Lleó, Alberto
Fortea, Juan
Alcolea, Daniel
Clarimon, Jordi
Nalls, Mike 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 J.
Torkamani, Ali
Singleton, Andrew B.
Ryten, Mina
Dickson, Dennis W.
Chiò, Adriano
Ross, Owen A.
Gibbs, J. Raphael
Dalgard, Clifton L.
Traynor, Bryan J.
Scholz, Sonja W.
Source :
Nature Genetics; March 2021, Vol. 53 Issue: 3 p294-303, 10p
Publication Year :
2021

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.

Details

Language :
English
ISSN :
10614036 and 15461718
Volume :
53
Issue :
3
Database :
Supplemental Index
Journal :
Nature Genetics
Publication Type :
Periodical
Accession number :
ejs55352360
Full Text :
https://doi.org/10.1038/s41588-021-00785-3