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Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

Title: Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture
Authors: Chia, R; Sabir, MS; Bandres-Ciga, S; Saez-Atienzar, S; Reynolds, RH; Gustavsson, E; Walton, RL; Ahmed, S; Viollet, C; Ding, J; Makarious, MB; Diez-Fairen, M; Portley, MK; Shah, Z; Abramzon, Y; Hernandez, DG; Blauwendraat, C; Stone, DJ; Eicher, J; Parkkinen, L; Ansorge, O; Clark, L; Honig, LS; Marder, K; Lemstra, A; St George-Hyslop, P; Londos, E; Morgan, K; Lashley, T; Warner, TT; Jaunmuktane, Z; Galasko, D; Santana, I; Tienari, PJ; Myllykangas, L; Oinas, M; Cairns, NJ; Morris, JC; Halliday, GM; Van Deerlin, VM; Trojanowski, JQ; Grassano, M; Calvo, A; Mora, G; Canosa, A; Floris, G; Bohannan, RC; Brett, F; Gan-Or, Z; Geiger, JT; Moore, A; May, P; Krüger, R; Goldstein, DS; Lopez, G; Tayebi, N; Sidransky, E; American Genome Center; Norcliffe-Kaufmann, L; Palma, J-A; Kaufmann, H; Shakkottai, VG; Perkins, M; Newell, KL; Gasser, T; Schulte, C; Landi, F; Salvi, E; Cusi, D; Masliah, E; Kim, RC; Caraway, CA; Monuki, ES; Brunetti, M; Dawson, TM; Rosenthal, LS; Albert, MS; Pletnikova, O; Troncoso, JC; Flanagan, ME; Mao, Q; Bigio, EH; Rodríguez-Rodríguez, E; Infante, J; Lage, C; González-Aramburu, I; Sanchez-Juan, P; Ghetti, B; Keith, J; Black, SE; Masellis, M; Rogaeva, E; Duyckaerts, C; Brice, A; Lesage, S; Xiromerisiou, G; Barrett, MJ; Tilley, BS; Gentleman, S; Logroscino, G; Serrano, GE; Beach, TG; McKeith, IG; Thomas, AJ; Attems, J; Morris, CM; Palmer, L; Love, S; Troakes, C; Al-Sarraj, S; Hodges, AK; Aarsland, D; Klein, G; Kaiser, SM; Woltjer, R; Pastor, P; Bekris, LM; Leverenz, JB; Besser, LM; Kuzma, A; Renton, AE; Goate, A; Bennett, DA; Scherzer, CR; Morris, HR; Ferrari, R; Albani, D; Pickering-Brown, S; Faber, K; Kukull, WA; Morenas-Rodriguez, E; Lleó, A; Fortea, J; Alcolea, D; Clarimon, J; Nalls, MA; Ferrucci, L; Resnick, SM; Tanaka, T; Foroud, TM; Graff-Radford, NR; Wszolek, ZK; Ferman, T; Boeve, BF; Hardy, JA; Topol, EJ; Torkamani, A; Singleton, AB; Ryten, M; Dickson, DW; Chiò, A; Ross, OA; Gibbs, JR; Dalgard, CL; Traynor, BJ; Scholz, SW
Source: Nature Genetics , 53 pp. 294-30353. (2021)
Publication Year: 2021
Collection: University College London: UCL Discovery
Description: 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 disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.
Document Type: article in journal/newspaper
File Description: text
Language: English
Relation: https://discovery.ucl.ac.uk/id/eprint/10123624/1/Lashley_LBD_manuscript_revision.pdf; https://discovery.ucl.ac.uk/id/eprint/10123624/
Availability: https://discovery.ucl.ac.uk/id/eprint/10123624/1/Lashley_LBD_manuscript_revision.pdf; https://discovery.ucl.ac.uk/id/eprint/10123624/
Rights: open
Accession Number: edsbas.CC2242A9
Database: BASE