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Genome-wide association analysis of Dementia with Lewy bodies reveals unique genetic architecture
| Content Provider | Semantic Scholar |
|---|---|
| Author | Guerreiro, Rita Ross, Owen A. Kun-Rodrigues, Celia Hernandez, Dena G. Orme, Tatiana Eicher, John D. Shepherd, Claire E. Parkkinen, Laura Darwent, Lee Heckman, Michael G. Scholz, Sonja W. Troncoso, Juan C. Pletniková, Olga Ansorge, Olaf Clarimon, Jordi Lleó, Alberto Morenas-Rodríguez, Estrella Clark, Lorraine Honig, Lawrence S. Marder, Karen S. Lemstra, Afina W. Rogaeva, Ekaterina A. Peter St. George-Hyslop Londos, Elisabet Zetterberg, Henrik Barber, Imelda S. Braae, Anne Brown, Kristelle S. Morgan, Kevin Troakes, Claire Al-Sarraj, Safa Lashley, Tammaryn Holton, Janice L. Compta, Yaroslau Deerlin, Vivianna M. Van Serrano, Geidy E. Beach, Thomas G. Lesage, Suzanne Galasko, Douglas R. Masliah, Eliezer Santana, Isabel Pastor, Pau Diez-Fairen, Monica Aguilar, Miquel Tienari, Pentti J. Myllykangas, Liisa Oinas, Minna Revesz, T. Lees, Andrew Boeve, Brad Petersen, Ronald C. Ferman, Tanis J. Escott-Price, Valentina Graff-Radford, Neill R. Cairns, Nigel J. Morris, John C. Pickering-Brown, Stuart Mann, David Halliday, Glenda M. Hardy, John Edward Trojanowski, John Q. Dickson, Dennis W. Singleton, Andrew B. Stone, David Brás, José Cascais |
| Copyright Year | 2017 |
| Abstract | Background: Dementia with Lewy Bodies (DLB) is the second most common form of dementia in the elderly but has been overshadowed in the research field, due in part, to similarities between DLB, Parkinson's (PD) and Alzheimer’s diseases (AD). This overlap complicates clinical care in that an accurate diagnosis is not always straightforward, and suggests that these diseases may share common aetiology. We have recently shown that loci implicated in susceptibility to PD and AD also play a role in DLB and that the proportion of genetic correlation between these diseases is very similar, when the major risk locus, APOE, is excluded. These results demonstrate that not only is DLB related to these more common diseases from a purely genetic perspective, but also, that DLB has a strong and quantifiable genetic component. Methods: Here we have performed the first large-scale genome-wide association study of DLB in a combined cohort of 6,197 samples. We exploited the recently established Haplotype Reference Consortium panel as the basis for imputation to a total of 8.4 million high-quality imputed genotypes and performed independent replication and a meta-analysis of significant and suggestive results. Findings: Results confirm previously reported associations (APOE, SNCA, GBA) and provide genome-wide significant signals for two novel loci (BCL7C/STX1B and CNTN1), in addition to several loci with suggestive levels of association. Additionally, using the genome-wide SNP data we estimate the heritable component of DLB to be approximately 36%. Interpretation: These results allow us to start to characterize, for the first time, the role of common genomic variability in DLB. They show unequivocally that common genetic variability plays a role in this disease, that this variability is, to some extent, shared with PD and AD and suggest a unique genetic risk profile in this disease. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://eprints.nottingham.ac.uk/48193/8/2017_DLB_GWAS_draft_for_circulation.pdf |
| Alternate Webpage(s) | http://orca-mwe.cf.ac.uk/107872/1/Binder1%20-Dementia%20with%20Lewy%20bodies.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
