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 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

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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).

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

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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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

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

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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.}",

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doi = "10.1038/ncomms8247",

language = "English (US)",

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journal = "Nature communications",

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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).

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

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