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 BeecherEvan 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

*Corresponding author for this work

Research output: Contribution to journalArticle

74 Citations (Scopus)

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 languageEnglish (US)
Article number7247
JournalNature communications
Volume6
DOIs
StatePublished - Jun 16 2015

Fingerprint

Progressive Supranuclear Palsy
degeneration
genome
Genome-Wide Association Study
Oligodendroglia
Myelin Sheath
Genes
myelin
Polymorphism
Single Nucleotide Polymorphism
Nucleotides
Long Noncoding RNA
Proteins
polymorphism
nucleotides
proteins
Neurodegenerative Diseases
Cognition
Meta-Analysis
Autopsy

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Kouri, N., Ross, O. A., Dombroski, B., Younkin, C. S., Serie, D. J., Soto-Ortolaza, A., ... Dickson, D. W. (2015). Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy. Nature communications, 6, [7247]. https://doi.org/10.1038/ncomms8247
Kouri, Naomi ; Ross, Owen A. ; Dombroski, Beth ; Younkin, Curtis S. ; Serie, Daniel J. ; Soto-Ortolaza, Alexandra ; Baker, Matthew ; Finch, Ni Cole A. ; Yoon, Hyejin ; Kim, Jungsu ; Fujioka, Shinsuke ; Mclean, Catriona A. ; Ghetti, Bernardino ; Spina, Salvatore ; Cantwell, Laura B. ; Farlow, Martin R. ; Grafman, Jordan ; Huey, Edward D. ; Ryung Han, Mi ; Beecher, Sherry ; Geller, Evan T. ; Kretzschmar, Hans A. ; Roeber, Sigrun ; Gearing, Marla ; Juncos, Jorge L. ; Vonsattel, Jean Paul G. ; Van Deerlin, Vivianna M. ; Grossman, Murray ; Hurtig, Howard I. ; Gross, Rachel G. ; Arnold, Steven E. ; Trojanowski, John Q. ; Lee, Virginia M. ; Wenning, Gregor K. ; White, Charles L. ; Höglinger, Günter U. ; Müller, Ulrich ; Devlin, Bernie ; Golbe, Lawrence I. ; Crook, Julia ; Parisi, Joseph E. ; Boeve, Bradley F. ; Josephs, Keith A. ; Wszolek, Zbigniew K. ; Uitti, Ryan J. ; Graff-Radford, Neill R. ; Litvan, Irene ; Younkin, Steven G. ; Wang, Li San ; Ertekin-Taner, Nilüfer ; Rademakers, Rosa ; Hakonarsen, Hakon ; Schellenberg, Gerard D. ; Dickson, Dennis W. / Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy. In: Nature communications. 2015 ; Vol. 6.
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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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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

Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy. / Kouri, Naomi; Ross, Owen A.; Dombroski, Beth; Younkin, Curtis S.; Serie, Daniel J.; Soto-Ortolaza, Alexandra; Baker, Matthew; Finch, Ni Cole A.; Yoon, Hyejin; Kim, Jungsu; Fujioka, Shinsuke; Mclean, Catriona A.; Ghetti, Bernardino; Spina, Salvatore; Cantwell, Laura B.; Farlow, Martin R.; Grafman, Jordan; Huey, Edward D.; Ryung Han, Mi; Beecher, Sherry; Geller, Evan T.; Kretzschmar, Hans A.; Roeber, Sigrun; Gearing, Marla; Juncos, Jorge L.; Vonsattel, Jean Paul G.; Van Deerlin, Vivianna M.; Grossman, Murray; Hurtig, Howard I.; Gross, Rachel G.; Arnold, Steven E.; Trojanowski, John Q.; Lee, Virginia M.; Wenning, Gregor K.; White, Charles L.; Höglinger, Günter U.; Müller, Ulrich; Devlin, Bernie; Golbe, Lawrence I.; Crook, Julia; Parisi, Joseph E.; Boeve, Bradley F.; Josephs, Keith A.; Wszolek, Zbigniew K.; Uitti, Ryan J.; Graff-Radford, Neill R.; Litvan, Irene; Younkin, Steven G.; Wang, Li San; Ertekin-Taner, Nilüfer; Rademakers, Rosa; Hakonarsen, Hakon; Schellenberg, Gerard D.; Dickson, Dennis W.

In: Nature communications, Vol. 6, 7247, 16.06.2015.

Research output: Contribution to journalArticle

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).

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