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Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into the complex genetic architecture
Chia, Ruth; Sabir, Marya S.; Bandres-Ciga, Sara et al.


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Keywords :
Lewy body dementia; whole-genome sequencing; GBA
Abstract :
[en] 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 and Parkinson’s disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.Competing Interest StatementThomas G. Beach is a consultant for Prothena, Vivid Genomics and Avid Radiopharmaceuticals. He is a scientific advisory board member for Vivid Genomics. John A. Hardy, Huw R. Morris, Stuart Pickering-Brown, Andrew B. Singleton, and Bryan J. Traynor hold US, EU and Canadian patents on the clinical testing and therapeutic intervention for the hexanucleotide repeat expansion of C9orf72. Michael A. Nalls is supported by a consulting contract between Data Tecnica International and the National Institute on Aging, NIH, Bethesda, MD, USA; as a possible conflict of interest Dr. Nalls also consults for Neuron23 Inc., Lysosomal Therapeutics Inc., Illumina Inc., the Michael J. Fox Foundation and Vivid Genomics among others. Jose A. Palma is an editorial board member of Movement Disorders, Parkinsonism & Related Disorders, BMC Neurology, and Clinical Autonomic Research. Bradley F. Boeve, James Leverenz, and Sonja W. Scholz serve on the Scientific Advisory Council of the Lewy Body Dementia Association. Sonja W. Scholz is an editorial board member for the Journal of Parkinson's Disease. Bryan J. Traynor is an editorial board member for JAMA Neurology; Journal of Neurology, Neurosurgery, and Psychiatry; Brain; and Neurobiology of Aging. Zbigniew K. Wszolek serves as a principal investigator or co-principal investigator on Abbvie, Inc. (M15-562 and M15-563), Biogen, Inc. (228PD201) grant, and Biohaven Pharmaceuticals, Inc. (BHV4157-206 and BHV3241-301). Zbigniew K. Wszolek serves as the principal investigator of the Mayo Clinic American Parkinson Disease Association (APDA) Information and Referral Center, and as co-principal investigator of the Mayo Clinic APDA Center for Advanced Research. All other authors report no competing interests.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Chia, Ruth;  1Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
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  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Krüger, Rejko ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience
Goldstein, David
Lopez, Grisel
Tayebi, Nahid
Sidransky, Ellen
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.
More authors (145 more) Less
Language :
Title :
Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into the complex genetic architecture
Publication date :
06 July 2020
Publisher :
Cold Spring Harbor Laboratory
Focus Area :
Systems Biomedicine
Available on ORBilu :
since 16 November 2020


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