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

Naomi Kouri(Jacksonville College), Owen A. Ross(Jacksonville College), Beth A. Dombroski(University of Pennsylvania), Curtis Younkin(Jacksonville College), Daniel Serie(Jacksonville College), Alexandra I. Soto‐Ortolaza(Jacksonville College), Matthew Baker(Jacksonville College), Ni Cole A. Finch(Jacksonville College), Hyejin Yoon(Jacksonville College), Jungsu Kim(Jacksonville College), Shinsuke Fujioka(Jacksonville College), Catriona McLean(Mental Health Research Institute), Bernardino Ghetti(Indiana University School of Medicine), Salvatore Spina(Indiana University School of Medicine), Laura B. Cantwell(University of Pennsylvania), Martin R. Farlow(Indiana University School of Medicine), Jordan Grafman(Northwestern University), Edward D. Huey(Columbia University), Mi Ryung Han(University of Pennsylvania), Sherry Beecher(University of Pennsylvania), Evan Geller(University of Pennsylvania), Hans A. Kretzschmar(Jacksonville College), Sigrun Roeber(Ludwig-Maximilians-Universität München), Marla Gearing(Emory University), Jorge L. Juncos(Emory University), Jean Paul Vonsattel(Columbia University), Vivianna M. Van Deerlin(University of Pennsylvania), Murray Grossman(University of Pennsylvania Health System), Howard I. Hurtig(University of Pennsylvania Health System), Owen A. Ross(University of Pennsylvania Health System), Steven E. Arnold(University of Pennsylvania), John Q. Trojanowski(University of Pennsylvania), Virginia M. Lee(University of Pennsylvania), Gregor K. Wenning(Innsbruck Medical University), Charles L. White(The University of Texas Southwestern Medical Center), Günter U. Höglinger(Philipps University of Marburg), Ulrich Müller(Justus-Liebig-Universität Gießen), Bernie Devlin(University of Pittsburgh), Lawrence I. Golbe(Rutgers, The State University of New Jersey), Julia E. Crook(Jacksonville College), Joseph E. Parisi(Mayo Clinic), Bradley F. Boeve(Mayo Clinic), Keith A. Josephs(Mayo Clinic), Zbigniew K. Wszołek(Mayo Clinic in Florida), Ryan J. Uitti(Mayo Clinic in Florida), Neill R. Graff‐Radford(Mayo Clinic in Florida), Irene Litvan(University of California San Diego), Steven G. Younkin(Jacksonville College), Li-San Wang(University of Pennsylvania), Nilüfer Ertekin‐Taner(Jacksonville College), Rosa Rademakers(Jacksonville College), Hakon Hakonarsen(Children's Hospital of Philadelphia), Gerard D. Schellenberg(University of Pennsylvania), Dennis W. Dickson(Jacksonville College)
Nature Communications
June 16, 2015
10.1038/ncomms8247
Cited by 241Open Access
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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; 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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