title: Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy.
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).
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Naomi
authors.identifier: http://orcid.org/0000-0002-6841-9882
authors.initials: N
authors.lastname: Kouri
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Dombroski
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.|Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Curtis S
authors.initials: CS
authors.lastname: Younkin
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Serie
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Soto-Ortolaza
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Baker
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Ni Cole A
authors.initials: NCA
authors.lastname: Finch
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Yoon
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Jungsu
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Fujioka
authors.affiliation: Victorian Brain Bank Network, Mental Health Research Institute, Parksville, Victoria 3052, Australia.
authors.forename: Catriona A
authors.initials: CA
authors.lastname: McLean
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Spina
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Cantwell
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Farlow
authors.affiliation: Cognitive Neuroscience Laboratory, Brain Injury Research, Rehabilitation Institute of Chicago, Chicago, Illinois 60611, USA.|Department of Physical Medicine and Rehabilitation, Northwestern University, Illinois 60208, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Grafman
authors.affiliation: Departments of Psychiatry and Neurology, Columbia University, New York, New York10027, USA.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Huey
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Mi
authors.initials: M
authors.lastname: Ryung Han
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Beecher
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Evan T
authors.initials: ET
authors.lastname: Geller
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
authors.affiliation: Institut for Neuropathology and Prion Research and Brain Net Germany, Ludwig-Maximilians-Universität, Munich 80539, Germany.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Roeber
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30307, USA.
authors.forename: Marla
authors.initials: M
authors.lastname: Gearing
authors.affiliation: Department of Neurology, Emory University, Atlanta, Georgia 30307, USA.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Juncos
authors.affiliation: Department of Pathology and the Taub Institute for Research on Alzheimer's disease and the Aging Brain, Columbia University, New York, New York 10027, USA.
authors.forename: Jean Paul G
authors.initials: JPG
authors.lastname: Vonsattel
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Vivianna M
authors.identifier: http://orcid.org/0000-0002-7400-9097
authors.initials: VM
authors.lastname: Van Deerlin
authors.affiliation: Department of Neurology, University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
authors.affiliation: Department of Neurology, University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Hurtig
authors.affiliation: Department of Neurology, University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Rachel G
authors.initials: RG
authors.lastname: Gross
authors.affiliation: Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Lee
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck 6020, Austria.
authors.forename: Gregor K
authors.initials: GK
authors.lastname: Wenning
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: White
authors.affiliation: Department of Neurology, Technical University Munich, 81377 Munich, Germany.|Department of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), 81677 Munich, Germany.|Department of Neurology, Philipps University, 35033 Marburg, Germany.
authors.forename: Günter U
authors.initials: GU
authors.lastname: Höglinger
authors.affiliation: Institut for Humangenetik, Justus-Liebig-Universität, Giessen 35390, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Müller
authors.affiliation: Department of Human Genetics, University of Pittsburgh, Pittsburg, Pennsylvania 15260, USA.
authors.forename: Bernie
authors.initials: B
authors.lastname: Devlin
authors.affiliation: Department of Neurology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901, USA.
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Golbe
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.|Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Crook
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parisi
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Josephs
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, Florida 32224, USA.
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, Florida 32224, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Uitti
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, Florida 32224, USA.
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Litvan
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Younkin
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Li-San
authors.initials: LS
authors.lastname: Wang
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.|Department of Neurology, Mayo Clinic, Jacksonville, Florida 32224, USA.
authors.forename: Nilüfer
authors.initials: N
authors.lastname: Ertekin-Taner
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.affiliation: Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarsen
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Schellenberg
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
authors.forename: Dennis W
authors.identifier: http://orcid.org/0000-0001-7189-7917
authors.initials: DW
authors.lastname: Dickson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001480:Basal Ganglia Diseases / Q000235:genetics*; D016022:Case-Control Studies; D002540:Cerebral Cortex; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009185:Myelin Proteins / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding / Q000235:genetics*; D020837:SOS1 Protein / Q000235:genetics*; D013494:Supranuclear Palsy, Progressive / Q000235:genetics*; D055815:Young Adult; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; C560487:MOBP protein, human; D009185:Myelin Proteins; D062085:RNA, Long Noncoding; D020837:SOS1 Protein; D016875:tau Proteins; C513406:KIF13B protein, human; D016547:Kinesins