| 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; American Genome Center; International LBD Genomics Consortium; International ALS/FTD Consortium; PROSPECT Consortium; Topol, E; Torkamani, A; Tienari, P; Foroud, TM; Ghetti, B; Landers, JE; Ryten, M; Morris, HR; Hardy, JA; Mazzini, L; D'Alfonso, S; Moglia, C; Calvo, A; Serrano, GE; Beach, TG; Ferman, T; Graff-Radford, NR; Boeve, BF; Wszolek, ZK; Dickson, DW; Chiò, A; Bennett, DA; De Jager, PL; Ross, OA; Dalgard, CL; Gibbs, JR; Traynor, BJ; Scholz, SW |
| Publisher Information: |
Elsevier |
| Publication Year: |
2023 |
| Collection: |
Imperial College London: Spiral |
| Subject Geographic: |
United States |
| 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 |
| Language: |
English |
| Relation: |
Cell Genomics; http://hdl.handle.net/10044/1/111361 |
| DOI: |
10.1016/j.xgen.2023.100316 |
| Availability: |
http://hdl.handle.net/10044/1/111361; https://doi.org/10.1016/j.xgen.2023.100316 |
| Rights: |
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). ; https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.203F2F57 |
| Database: |
BASE |