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; Evan T. Geller; Hans A. Kretzschmar; Sigrun Roeber; Marla Gearing; Jorge L. Juncos; Jean Paul G. Vonsattel; Vivianna M. Van Deerlin; Murray Grossman; Howard I. Hurtig; Rachel G. Gross; Steven E. Arnold; John Q. Trojanowski; Virginia M. Lee; Gregor K. Wenning; Charles L. White; Günter U. Höglinger; Ulrich Müller; Bernie Devlin; Lawrence I. Golbe; Julia Crook; Joseph E. Parisi; Bradley F. Boeve; Keith A. Josephs; Zbigniew K. Wszolek; Ryan J. Uitti; Neill R. Graff-Radford; Irene Litvan; Steven G. Younkin; Li San Wang; Nilüfer Ertekin-Taner; Rosa Rademakers; Hakon Hakonarsen; Gerard D. Schellenberg; Dennis W. Dickson

doi:10.1038/ncomms8247

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

Evan T. Geller, Hans A. Kretzschmar, Sigrun Roeber, Marla Gearing, Jorge L. Juncos, Jean Paul G. Vonsattel, Vivianna M. Van Deerlin, Murray Grossman, Howard I. Hurtig, Rachel G. Gross, Steven E. Arnold, John Q. Trojanowski, Virginia M. Lee, Gregor K. Wenning, Charles L. White, Günter U. Höglinger, Ulrich Müller, Bernie Devlin, Lawrence I. Golbe, Julia Crook, Joseph E. Parisi, Bradley F. Boeve, Keith A. Josephs, Zbigniew K. Wszolek, Ryan J. Uitti, Neill R. Graff-Radford, Irene Litvan, Steven G. Younkin, Li San Wang, Nilüfer Ertekin-Taner, Rosa Rademakers, Hakon Hakonarsen, Gerard D. Schellenberg, Dennis W. Dickson

Department of Neurology

Mayo Clinic in Jacksonville, Florida
The University of Pennsylvania
The Florey Institute of Neuroscience and Mental Health
Indiana University School of Medicine
Rehabilitation Institute of Chicago
Northwestern University
Columbia University
University of Munich
Emory University School of Medicine
University of Pennsylvania
University of Pennsylvania
Medical University Innsbruck
University of Texas at Dallas
German Center for Neurodegenerative Diseases (DZNE)
Philipps-Universität Marburg
Justus-Liebig-Universität Gießen
University of Pittsburgh
UMDNJ-Robert Wood Johnson Med. Sch.
Mayo Clinic
Department of Neurosciences
Children's Hospital of Philadelphia

Research output: Contribution to journal › Article › peer-review

169 Scopus citations

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).

Original language	English
Article number	7247
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8247
State	Published - 16 Jun 2015

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10.1038/ncomms8247

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Kouri, N., Ross, O. A., Dombroski, B., Younkin, C. S., Serie, D. J., Soto-Ortolaza, A., Baker, M., Finch, N. C. A., Yoon, H., Kim, J., Fujioka, S., Mclean, C. A., Ghetti, B., Spina, S., Cantwell, L. B., Farlow, M. R., Grafman, J., Huey, E. D., Ryung Han, M., ... Dickson, D. W. (2015). Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy. Nature Communications, 6, Article 7247. https://doi.org/10.1038/ncomms8247

@article{2b07cc44033d4ec09ba134c2690d12de,

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).",

author = "Naomi Kouri and Ross, \{Owen A.\} and Beth Dombroski and Younkin, \{Curtis S.\} and Serie, \{Daniel J.\} and Alexandra Soto-Ortolaza and Matthew Baker and Finch, \{Ni Cole A.\} and Hyejin Yoon and Jungsu Kim and Shinsuke Fujioka and Mclean, \{Catriona A.\} and Bernardino Ghetti and Salvatore Spina and Cantwell, \{Laura B.\} and Farlow, \{Martin R.\} and Jordan Grafman and Huey, \{Edward D.\} and \{Ryung Han\}, Mi and Sherry Beecher and Geller, \{Evan T.\} and Kretzschmar, \{Hans A.\} and Sigrun Roeber and Marla Gearing and Juncos, \{Jorge L.\} and Vonsattel, \{Jean Paul G.\} and \{Van Deerlin\}, \{Vivianna M.\} and Murray Grossman and Hurtig, \{Howard I.\} and Gross, \{Rachel G.\} and Arnold, \{Steven E.\} and Trojanowski, \{John Q.\} and Lee, \{Virginia M.\} and Wenning, \{Gregor K.\} and White, \{Charles L.\} and H{\"o}glinger, \{G{\"u}nter U.\} and Ulrich M{\"u}ller and Bernie Devlin and Golbe, \{Lawrence I.\} and Julia Crook and Parisi, \{Joseph E.\} and Boeve, \{Bradley F.\} and Josephs, \{Keith A.\} and Wszolek, \{Zbigniew K.\} and Uitti, \{Ryan J.\} and Graff-Radford, \{Neill R.\} and Irene Litvan and Younkin, \{Steven G.\} and Wang, \{Li San\} and Nil{\"u}fer Ertekin-Taner and Rosa Rademakers and Hakon Hakonarsen and Schellenberg, \{Gerard D.\} and Dickson, \{Dennis W.\}",

year = "2015",

month = jun,

day = "16",

doi = "10.1038/ncomms8247",

language = "English",

volume = "6",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

}

Kouri, N, Ross, OA, Dombroski, B, Younkin, CS, Serie, DJ, Soto-Ortolaza, A, Baker, M, Finch, NCA, Yoon, H, Kim, J, Fujioka, S, Mclean, CA, Ghetti, B, Spina, S, Cantwell, LB, Farlow, MR, Grafman, J, Huey, ED, Ryung Han, M, Beecher, S, Geller, ET, Kretzschmar, HA, Roeber, S, Gearing, M, Juncos, JL, Vonsattel, JPG, Van Deerlin, VM, Grossman, M, Hurtig, HI, Gross, RG, Arnold, SE, Trojanowski, JQ, Lee, VM, Wenning, GK, White, CL, Höglinger, GU, Müller, U, Devlin, B, Golbe, LI, Crook, J, Parisi, JE, Boeve, BF, Josephs, KA, Wszolek, ZK, Uitti, RJ, Graff-Radford, NR, Litvan, I, Younkin, SG, Wang, LS, Ertekin-Taner, N, Rademakers, R, Hakonarsen, H, Schellenberg, GD & Dickson, DW 2015, 'Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy', Nature Communications, vol. 6, 7247. https://doi.org/10.1038/ncomms8247

TY - JOUR

T1 - Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy

AU - Kouri, Naomi

AU - Ross, Owen A.

AU - Dombroski, Beth

AU - Younkin, Curtis S.

AU - Serie, Daniel J.

AU - Soto-Ortolaza, Alexandra

AU - Baker, Matthew

AU - Finch, Ni Cole A.

AU - Yoon, Hyejin

AU - Kim, Jungsu

AU - Fujioka, Shinsuke

AU - Mclean, Catriona A.

AU - Ghetti, Bernardino

AU - Spina, Salvatore

AU - Cantwell, Laura B.

AU - Farlow, Martin R.

AU - Grafman, Jordan

AU - Huey, Edward D.

AU - Ryung Han, Mi

AU - Beecher, Sherry

AU - Geller, Evan T.

AU - Kretzschmar, Hans A.

AU - Roeber, Sigrun

AU - Gearing, Marla

AU - Juncos, Jorge L.

AU - Vonsattel, Jean Paul G.

AU - Van Deerlin, Vivianna M.

AU - Grossman, Murray

AU - Hurtig, Howard I.

AU - Gross, Rachel G.

AU - Arnold, Steven E.

AU - Trojanowski, John Q.

AU - Lee, Virginia M.

AU - Wenning, Gregor K.

AU - White, Charles L.

AU - Höglinger, Günter U.

AU - Müller, Ulrich

AU - Devlin, Bernie

AU - Golbe, Lawrence I.

AU - Crook, Julia

AU - Parisi, Joseph E.

AU - Boeve, Bradley F.

AU - Josephs, Keith A.

AU - Wszolek, Zbigniew K.

AU - Uitti, Ryan J.

AU - Graff-Radford, Neill R.

AU - Litvan, Irene

AU - Younkin, Steven G.

AU - Wang, Li San

AU - Ertekin-Taner, Nilüfer

AU - Rademakers, Rosa

AU - Hakonarsen, Hakon

AU - Schellenberg, Gerard D.

AU - Dickson, Dennis W.

PY - 2015/6/16

Y1 - 2015/6/16

N2 - 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).

AB - 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).

UR - https://www.scopus.com/pages/publications/84935832302

U2 - 10.1038/ncomms8247

DO - 10.1038/ncomms8247

M3 - Article

C2 - 26077951

AN - SCOPUS:84935832302

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 7247

ER -

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

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