2021
Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture
Authors:
Chia, R., Sabir, M.S., Bandres-Ciga, S. Aarsland D, Abramzon Y, Adeleye A, Ahmed S, Alba C, Albani D, Albert MS, Alcolea D, Al-Sarraj S, Ansorge O, Attems J, Bacikova D, Barrett MJ, Beach TG, Bekris LM, Bennett DA, Besser LM, Bigio EH, Black SE, Blauwendraat C, Boeve BF, Bohannan RC, Brett F, Brice A, Brunetti M, Cairns NJ, Calvo A, Canosa A, Caraway CA, Chiò A, Clarimon J, Clark L, Cusi D, Dalgard CL, Dawson TM, Dickson DW, Diez-Fairen M, Ding J. Duyckaerts C, Eicher J, Faber K, Ferman T, Ferrari R, Ferrucci L. Flanagan ME, Floris G, Foroud TM, Fortea J, Galasko D, Gan-Or Z. Gasser T, Geiger JT, Gentleman S, Ghetti B, Gibbs JR, Goate A, Goldstein DS, González-Aramburu I, Graff-Radford NR, Grassano M, Gustavsson E, Halliday GM, Hardy JA, Hernandez DG, Hodges AK, Honig LS, Hupalo DN, Infante J, Jaunmuktane Z, Kaiser SM, Kaufmann H, Keith J, Kim RC, Klein G, Krüger R, Kukull WA, Kuzma A, Lage C, Landi F, Lashley T, Lemstra A, Lesage S, Leverenz JB, Lleó A, Logroscino G, Londos E, Lopez G, Lott N, Love S, Makarious MB, Mao O, Marder K, Masellis M, Masliah E, May P, McGrath Martinez E, McKeith IG, Meila Tuck, Monuki ES, Moore A, Mora G, Morenas-Rodriguez E, Morgan K, Morris CM, Morris HR, Morris JC, Myllykangas L, Nalls MA, Newell KL, Norcliffe-Kaufmann L, Oinas M, Palma JA, Palmer L, Parkkinen L, Pastor P, Perkins M, Pickering-Brown S, Pletnikova O, Pollard HB, Portley MK, Renton AE, Resnick SM, Reynolds RH, Rodríguez-Rodríguez E, Rogaeva E, Rosenthal LS, Ross OA, Ryten M, Saez-Atienzar S, Salvi E, Sanchez-Juan P, Santana I, Scherzer CR, Scholz SW, Schulte C, Serrano GE, Shah Z, Shakkottai VG, Sidransky E, Singh J, Singleton AB, Sotis AR, St George-Hyslop P, Stone DJ, Sukumar G, Tanaka T, Tayebi N, Thomas AJ, Tienari PJ, Tilley BS, Topol EJ, Torkamani A, Traynor BJ, Troakes C, Trojanowski JQ, Troncoso JC, Van Deerlin VM, Viollet C, Walton RL, Warner TT, Wilkerson MD, Woltjer R, Wszolek ZK, Xiromerisiou G, Zhang X
Journal:
Nature Genetics
Abstract
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.
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