학술논문
Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias
Document Type
article
Author
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; Jerez, Pilar Alvarez; 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; Soltis, Anthony R; Viollet, Coralie; Sukumar, Gauthaman; Alba, Camille; Lott, Nathaniel; Martinez, Elisa McGrath; Tuck, Meila; Singh, Jatinder; Bacikova, Dagmar; Zhang, Xijun; Hupalo, Daniel N; Adeleye, Adelani; Wilkerson, Matthew D; Pollard, Harvey B; Dalgard, Clifton L; Gan-Or, Ziv; Rogaeva, Ekaterina; Brice, Alexis; Lesage, Suzanne; Xiromerisiou, Georgia; Calvo, Andrea; Canosa, Antonio; Chio, Adriano; Logroscino, Giancarlo; Mora, Gabriele; Krüger, Reijko; May, Patrick; Alcolea, Daniel; Clarimon, Jordi; Fortea, Juan; Gonzalez-Aramburu, Isabel; Infante, Jon; Lage, Carmen; Lleó, Alberto; Pastor, Pau; Sanchez-Juan, Pascual; Brett, Francesca; Aarsland, Dag; Al-Sarraj, Safa; Attems, Johannes; Gentleman, Steve; Hardy, John A; Hodges, Angela K; Love, Seth; McKeith, Ian G; Morris, Christopher M; Morris, Huw R; Palmer, Laura; Pickering-Brown, Stuart; Ryten, Mina; Thomas, Alan J; Troakes, Claire; Barrett, Matthew J; Beach, Thomas G; Bekris, Lynn M; Bennett, David A; Boeve, Bradley F; Dickson, Dennis W; Faber, Kelley; Ferman, Tanis; Flanagan, Margaret E; Foroud, Tatiana M; Ghetti, Bernardino; Gibbs, J Raphael
Source
Cell Genomics. 3(6)
Subject
Language
Abstract
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.