| Title: |
Genome-wide structural variant analysis identifies risk loci for non-Alzheimer's dementias |
| Authors: |
Kaivola, K; Chia, R; Ding, J; Rasheed, M; Fujita, M; Menon, V; Walton, RL; Collins, RL; Billingsley, K; Brand, H; Talkowski, M; Zhao, X; Dewan, R; Stark, A; Ray, A; Solaiman, S; Alvarez Jerez, P; Malik, L; Dawson, TM; Rosenthal, LS; Albert, MS; Pletnikova, O; Troncoso, JC; Masellis, M; Keith, J; Black, SE; Ferrucci, L; Resnick, SM; Tanaka, T; Soltis, AR; Viollet, C; Sukumar, G; Alba, C; Lott, N; McGrath Martinez, E; Tuck, M; Singh, J; Bacikova, D; Zhang, X; Hupalo, DN; Adeleye, A; Wilkerson, MD; Pollard, HB; Dalgard, CL; Gan-Or, Z; Rogaeva, E; Brice, A; Lesage, S; Xiromerisiou, G; Calvo, A; Canosa, A; Chio, A; Logroscino, G; Mora, G; Krüger, R; May, P; Alcolea, D; Clarimon, J; Fortea, J; Gonzalez-Aramburu, I; Infante, J; Lage, C; Lleó, A; Pastor, P; Sanchez-Juan, P; Brett, F; Aarsland, D; Al-Sarraj, S; Attems, J; Gentleman, S; Hardy, JA; Hodges, AK; Love, S; McKeith, IG; Morris, CM; Morris, HR; Palmer, L; Pickering-Brown, S; Ryten, M; Thomas, AJ; Troakes, C; Barrett, MJ; Beach, TG; Bekris, LM; Bennett, DA; Boeve, BF; Dickson, DW; Faber, K; Ferman, T; Flanagan, ME; Foroud, TM; Ghetti, B; Gibbs, JR; Goate, A; Goldstein, DS; Graff-Radford, NR; Kaufmann, H; Kukull, WA; Leverenz, JB; Lopez, G |
| Source: |
Cell Genomics , 3 (6) , Article 100316. (2023) |
| Publisher Information: |
Elsevier BV |
| Publication Year: |
2023 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Lewy body dementia; frontotemporal dementia; amyotrophic lateral sclerosis; structural variant; genome-wide association study; resource; case-control study; non–Alzheimer's dementia |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10172559/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10172559/1/1-s2.0-S2666979X23000848-main.pdf; https://discovery.ucl.ac.uk/id/eprint/10172559/ |
| Rights: |
open |
| Accession Number: |
edsbas.8FC8FE9F |
| Database: |
BASE |