Journal article

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

Naomi Kouri, Owen A Ross, Beth Dombroski, Curtis S Younkin, Daniel J Serie, Alexandra Soto-Ortolaza, Matthew Baker, Ni Cole A Finch, Hyejin Yoon, Jungsu Kim, Shinsuke Fujioka, Catriona A McLean, Bernardino Ghetti, Salvatore Spina, Laura B Cantwell, Martin R Farlow, Jordan Grafman, Edward D Huey, Mi Ryung Han, Sherry Beecher Show all

NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2015

Abstract

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..

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Awarded by NIH


Awarded by Deutsche Forschungsgemeinschaft (DFG)



Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Awarded by NATIONAL INSTITUTE ON AGING


Funding Acknowledgements

We gratefully acknowledge support of patients and their families for participating in this study, as well as the Foundation for PSP vertical bar CBD and Related Brain Diseases, and the PSP Genetics Study Group. N.K. is supported by a post-doctoral fellowship from the Karin & Sten Mortstedt CBD Solutions AB. O.A.R. is supported by NIH P50 NS072187 and R01 NS078086. D.W.D. is supported by NIH P50 NS072187, P50 AG016574, R01 AG037491, as well as State of Florida Alzheimer's Disease Initiative and the Foundation for PSP vertical bar CBD and Related Brain Diseases. GDS is supported by NIH P01 AG017586 and grants from Foundation for PSP vertical bar CBD and Related Brain Diseases and Peebler PSP Research Foundation. N.E.-T. is supported by R01 AG032990, R01 NS080820, and P50 AG0016574. J.K. is supported by GHR Foundation. J.Q.T. is supported by NIH P30 AG10124, P01 AG17586, and P50 NS53488. B.G. is supported by NIH P30 AG10133. C.L.W. is supported by NIH P30 AG012300. G.U.H. is funded by the Deutsche Forschungsgemeinschaft (DFG: HO2402/6-2) and Bundesministerium fur Bildung und Forschung (BMBF: EpiPD). L.I.G. is supported by CBD Solutions, The Rainwater Charitable Foundation. and the American Parkinson's Disease Association. U.M. was supported by Foundation for PSP vertical bar CBD and Related Brain Diseases. I.L. is supported by MJFF, NIH, Foundation for PSP vertical bar CBD and Related Brain Diseases, and CBD Solutions. Z.K.W. is partially supported by the NIH P50 NS072187, the Mayo Clinic Center for Regenerative Medicine, Neuroscience Focused Research Team programme, and a gift from Carl Edward Bolch, Jr and Susan Bass Bolch.