Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy

Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associa...

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Detalles Bibliográficos
Autores principales: Kouri, Naomi, Ross, Owen A., Dombroski, Beth, Younkin, Curtis S., Serie, Daniel J., Soto-Ortolaza, Alexandra, Baker, Matthew, Finch, Ni Cole A., Yoon, Hyejin, Kim, Jungsu, Fujioka, Shinsuke, McLean, Catriona A., Ghetti, Bernardino, Spina, Salvatore, Cantwell, Laura B., Farlow, Martin R., Grafman, Jordan, Huey, Edward D., Ryung Han, Mi, Beecher, Sherry, Geller, Evan T., Kretzschmar, Hans A., Roeber, Sigrun, Gearing, Marla, Juncos, Jorge L., Vonsattel, Jean Paul G., Van Deerlin, Vivianna M., Grossman, Murray, Hurtig, Howard I., Gross, Rachel G., Arnold, Steven E., Trojanowski, John Q., Lee, Virginia M., Wenning, Gregor K., White, Charles L., Höglinger, Günter U., Müller, Ulrich, Devlin, Bernie, Golbe, Lawrence I., Crook, Julia, Parisi, Joseph E., Boeve, Bradley F., Josephs, Keith A., Wszolek, Zbigniew K., Uitti, Ryan J., Graff-Radford, Neill R., Litvan, Irene, Younkin, Steven G., Wang, Li-San, Ertekin-Taner, Nilüfer, Rademakers, Rosa, Hakonarsen, Hakon, Schellenberg, Gerard D., Dickson, Dennis W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469997/
https://www.ncbi.nlm.nih.gov/pubmed/26077951
http://dx.doi.org/10.1038/ncomms8247
Descripción
Sumario:Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P=1.42 × 10(−12)), 8p12 at lnc-KIF13B-1, a long non-coding RNA (rs643472; P=3.41 × 10(−8)), and 2p22 at SOS1 (rs963731; P=1.76 × 10(−7)). Testing for association of CBD with top progressive supranuclear palsy (PSP) GWAS single-nucleotide polymorphisms (SNPs) identified associations at MOBP (3p22; rs1768208; P=2.07 × 10(−7)) and MAPT H1c (17q21; rs242557; P=7.91 × 10(−6)). We previously reported SNP/transcript level associations with rs8070723/MAPT, rs242557/MAPT, and rs1768208/MOBP and herein identified association with rs963731/SOS1. We identify new CBD susceptibility loci and show that CBD and PSP share a genetic risk factor other than MAPT at 3p22 MOBP (myelin-associated oligodendrocyte basic protein).

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