[en] We characterized the role of structural variants, a largely unexplored type of genetic variation, in two non-Alzheimer’s dementias, namely Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced structural variant calling pipeline (GATK-SV) to short-read whole-genome sequence data from 5,213 European-ancestry cases and 4,132 controls. We discovered, replicated, and validated a deletion in TPCN1 as a novel risk locus for LBD and detected the known structural variants at the C9orf72 and MAPT loci as associated with FTD/ALS. We also identified rare pathogenic structural variants in both LBD and FTD/ALS. Finally, we assembled a catalog of structural variants that can be mined for new insights into the pathogenesis of these understudied forms of dementia.
Centre de recherche :
- Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) - Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) LIH - Luxembourg Institute of Health
Disciplines :
Neurologie Génétique & processus génétiques
Auteur, co-auteur :
Kaivola, Karri
Chia, Ruth
Ding, Jinhui
Rasheed, Memoona
Fujita, Masashi
Menon, Vilas
Walton, Ronald L.
Collins, Ryan L.
Billingsley, Kimberley
Brand, Harrison
Talkowski, Michael
Zhao, Xuefang
Dewan, Ramita
Stark, Ali
Ray, Anindita
Solaiman, Sultana
Alvarez Jerez, Pilar
Malik, Laksh
Dawson, Ted M.
Rosenthal, Liana S.
Albert, Marilyn S.
Pletnikova, Olga
Troncoso, Juan C.
Masellis, Mario
Keith, Julia
Black, Sandra E.
Ferrucci, Luigi
Resnick, Susan M.
Tanaka, Toshiko
Topol, Eric
Torkamani, Ali
Tienari, Pentti
Foroud, Tatiana M.
Ghetti, Bernardino
Landers, John E.
Ryten, Mina
Morris, Huw R.
Hardy, John A.
Mazzini, Letizia
D'Alfonso, Sandra
Moglia, Cristina
Calvo, Andrea
Serrano, Geidy E.
Beach, Thomas G.
Ferman, Tanis
Graff-Radford, Neill R.
Boeve, Bradley F.
Wszolek, Zbigniew K.
Dickson, Dennis W.
Chiò, Adriano
Bennett, David A.
De Jager, Philip L.
Ross, Owen A.
Dalgard, Clifton L.
Gibbs, J. Raphael
Traynor, Bryan J.
Scholz, Sonja W.
Soltis, Anthony R.
Viollet, Coralie
Sukumar, Gauthaman
Alba, Camille
Lott, Nathaniel
McGrath Martinez, Elisa
Tuck, Meila
Singh, Jatinder
Bacikova, Dagmar
Zhang, Xijun
Hupalo, Daniel N.
Adeleye, Adelani
Wilkerson, Matthew D.
Pollard, Harvey B.
Dalgard, Clifton L.
Black, Sandra E.
Gan-Or, Ziv
Keith, Julia
Masellis, Mario
Rogaeva, Ekaterina
Brice, Alexis
Lesage, Suzanne
Xiromerisiou, Georgia
Calvo, Andrea
Canosa, Antonio
Chio, Adriano
Logroscino, Giancarlo
Mora, Gabriele
KRÜGER, Rejko ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience
MAY, Patrick ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
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