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Nat Commun. 2015 Jun 16;6:7247. doi: 10.1038/ncomms8247.

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

Author information

1
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
2
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
3
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
4
Victorian Brain Bank Network, Mental Health Research Institute, Parksville, Victoria 3052, Australia.
5
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
6
Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
7
Cognitive Neuroscience Laboratory, Brain Injury Research, Rehabilitation Institute of Chicago, Chicago, Illinois 60611, USA.
8
Department of Physical Medicine and Rehabilitation, Northwestern University, Illinois 60208, USA.
9
Departments of Psychiatry and Neurology, Columbia University, New York, New York10027, USA.
10
Institut for Neuropathology and Prion Research and Brain Net Germany, Ludwig-Maximilians-Universität, Munich 80539, Germany.
11
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30307, USA.
12
Department of Neurology, Emory University, Atlanta, Georgia 30307, USA.
13
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.
14
Department of Neurology, University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104, USA.
15
Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
16
Department of Neurology, Innsbruck Medical University, Innsbruck 6020, Austria.
17
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
18
Department of Neurology, Technical University Munich, 81377 Munich, Germany.
19
Department of Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), 81677 Munich, Germany.
20
Department of Neurology, Philipps University, 35033 Marburg, Germany.
21
Institut for Humangenetik, Justus-Liebig-Universität, Giessen 35390, Germany.
22
Department of Human Genetics, University of Pittsburgh, Pittsburg, Pennsylvania 15260, USA.
23
Department of Neurology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901, USA.
24
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
25
Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA.
26
Department of Neurology, Mayo Clinic, Jacksonville, Florida 32224, USA.
27
Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.
28
Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.

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).

PMID:
26077951
PMCID:
PMC4469997
DOI:
10.1038/ncomms8247
[Indexed for MEDLINE]
Free PMC Article

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