Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy

Günter U. Höglinger, Nadine M. Melhem, Dennis W. Dickson, Patrick M A Sleiman, Li San Wang, Lambertus Klei, Rosa Rademakers, Rohan De Silva, Irene Litvan, David E. Riley, John C. Van Swieten, Peter Heutink, Zbigniew K. Wszolek, Ryan J. Uitti, Jana Vandrovcova, Howard I. Hurtig, Rachel G. Gross, Walter Maetzler, Stefano Goldwurm, Eduardo Tolosa & 116 others Barbara Borroni, Pau Pastor, Laura B. Cantwell, Mi Ryung Han, Allissa Dillman, Marcel P. Van Der Brug, J. Raphael Gibbs, Mark R. Cookson, Dena G. Hernandez, Andrew B. Singleton, Matthew J. Farrer, Chang En Yu, Lawrence I. Golbe, Tamas Revesz, John Hardy, Andrew J. Lees, Bernie Devlin, Hakon Hakonarson, Ulrich Müller, Gerard D. Schellenberg, Roger L. Albin, Elena Alonso, Angelo Antonini, Manuela Apfelbacher, Steven E. Arnold, Jesus Avila, Thomas G. Beach, Sherry Beecher, Daniela Berg, Thomas D. Bird, Nenad Bogdanovic, Agnita J W Boon, Yvette Bordelon, Alexis Brice, Herbert Budka, Margherita Canesi, Wang Zheng Chiu, Roberto Cilia, Carlo Colosimo, Peter P. De Deyn, Justo Garcãa De Yebenes, Laura Donker Kaat, Ranjan Duara, Alexandra Durr, Sebastiaan Engelborghs, Giovanni Fabbrini, Nicole A. Finch, Robyn Flook, Matthew P. Frosch, Carles Gaig, Douglas R. Galasko, Thomas Gasser, Marla Gearing, Evan T. Geller, Bernardino Ghetti, Neill R. Graff-Radford, Murray Grossman, Deborah A. Hall, Lili Naz Hazrati, Matthias Höllerhage, Joseph Jankovic, Jorge L. Juncos, Anna Karydas, Hans A. Kretzschmar, Isabelle Leber, Virginia M. Lee, Andrew P. Lieberman, Kelly E. Lyons, Claudio Mariani, Eliezer Masliah, Luke A. Massey, Catriona A. McLean, Nicoletta Meucci, Bruce L. Miller, Brit Mollenhauer, Jens C. Möller, Huw R. Morris, Chris Morris, Sean S. O'Sullivan, Wolfgang H. Oertel, Donatella Ottaviani, Alessandro Padovani, Rajesh Pahwa, Gianni Pezzoli, Stuart Pickering-Brown, Werner Poewe, Alberto Rabano, Alex Rajput, Stephen G. Reich, Gesine Respondek, Sigrun Roeber, Jonathan D. Rohrer, Owen A. Ross, Martin N. Rossor, Giorgio Sacilotto, William W. Seeley, Klaus Seppi, Laura Silveira-Moriyama, Salvatore Spina, Karin Srulijes, Peter St. George-Hyslop, Maria Stamelou, David G. Standaert, Silvana Tesei, Wallace W. Tourtellotte, Claudia Trenkwalder, Claire Troakes, John Q. Trojanowski, Juan C Troncoso, Vivianna M. Van Deerlin, Jean Paul G Vonsattel, Gregor K. Wenning, Charles L. White, Pia Winter, Chris Zarow, Anna L. Zecchinelli

Research output: Contribution to journalArticle

Abstract

Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP (cases) and 3,247 controls (stage 1) followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals (P <5 × 10-8) associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component.

Original languageEnglish (US)
Pages (from-to)699-705
Number of pages7
JournalNature Genetics
Volume43
Issue number7
DOIs
StatePublished - Jul 2011

Fingerprint

Tauopathies
Progressive Supranuclear Palsy
Membrane Fusion Proteins
Unfolded Protein Response
Genome-Wide Association Study
Movement Disorders
Brain Diseases
Myelin Sheath
Craniocerebral Trauma
Endoplasmic Reticulum
Sports
Single Nucleotide Polymorphism
Alzheimer Disease
Brain
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Höglinger, G. U., Melhem, N. M., Dickson, D. W., Sleiman, P. M. A., Wang, L. S., Klei, L., ... Zecchinelli, A. L. (2011). Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nature Genetics, 43(7), 699-705. https://doi.org/10.1038/ng.859

Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. / Höglinger, Günter U.; Melhem, Nadine M.; Dickson, Dennis W.; Sleiman, Patrick M A; Wang, Li San; Klei, Lambertus; Rademakers, Rosa; De Silva, Rohan; Litvan, Irene; Riley, David E.; Van Swieten, John C.; Heutink, Peter; Wszolek, Zbigniew K.; Uitti, Ryan J.; Vandrovcova, Jana; Hurtig, Howard I.; Gross, Rachel G.; Maetzler, Walter; Goldwurm, Stefano; Tolosa, Eduardo; Borroni, Barbara; Pastor, Pau; Cantwell, Laura B.; Han, Mi Ryung; Dillman, Allissa; Van Der Brug, Marcel P.; Gibbs, J. Raphael; Cookson, Mark R.; Hernandez, Dena G.; Singleton, Andrew B.; Farrer, Matthew J.; Yu, Chang En; Golbe, Lawrence I.; Revesz, Tamas; Hardy, John; Lees, Andrew J.; Devlin, Bernie; Hakonarson, Hakon; Müller, Ulrich; Schellenberg, Gerard D.; Albin, Roger L.; Alonso, Elena; Antonini, Angelo; Apfelbacher, Manuela; Arnold, Steven E.; Avila, Jesus; Beach, Thomas G.; Beecher, Sherry; Berg, Daniela; Bird, Thomas D.; Bogdanovic, Nenad; Boon, Agnita J W; Bordelon, Yvette; Brice, Alexis; Budka, Herbert; Canesi, Margherita; Chiu, Wang Zheng; Cilia, Roberto; Colosimo, Carlo; De Deyn, Peter P.; De Yebenes, Justo Garcãa; Kaat, Laura Donker; Duara, Ranjan; Durr, Alexandra; Engelborghs, Sebastiaan; Fabbrini, Giovanni; Finch, Nicole A.; Flook, Robyn; Frosch, Matthew P.; Gaig, Carles; Galasko, Douglas R.; Gasser, Thomas; Gearing, Marla; Geller, Evan T.; Ghetti, Bernardino; Graff-Radford, Neill R.; Grossman, Murray; Hall, Deborah A.; Hazrati, Lili Naz; Höllerhage, Matthias; Jankovic, Joseph; Juncos, Jorge L.; Karydas, Anna; Kretzschmar, Hans A.; Leber, Isabelle; Lee, Virginia M.; Lieberman, Andrew P.; Lyons, Kelly E.; Mariani, Claudio; Masliah, Eliezer; Massey, Luke A.; McLean, Catriona A.; Meucci, Nicoletta; Miller, Bruce L.; Mollenhauer, Brit; Möller, Jens C.; Morris, Huw R.; Morris, Chris; O'Sullivan, Sean S.; Oertel, Wolfgang H.; Ottaviani, Donatella; Padovani, Alessandro; Pahwa, Rajesh; Pezzoli, Gianni; Pickering-Brown, Stuart; Poewe, Werner; Rabano, Alberto; Rajput, Alex; Reich, Stephen G.; Respondek, Gesine; Roeber, Sigrun; Rohrer, Jonathan D.; Ross, Owen A.; Rossor, Martin N.; Sacilotto, Giorgio; Seeley, William W.; Seppi, Klaus; Silveira-Moriyama, Laura; Spina, Salvatore; Srulijes, Karin; St. George-Hyslop, Peter; Stamelou, Maria; Standaert, David G.; Tesei, Silvana; Tourtellotte, Wallace W.; Trenkwalder, Claudia; Troakes, Claire; Trojanowski, John Q.; Troncoso, Juan C; Van Deerlin, Vivianna M.; Vonsattel, Jean Paul G; Wenning, Gregor K.; White, Charles L.; Winter, Pia; Zarow, Chris; Zecchinelli, Anna L.

In: Nature Genetics, Vol. 43, No. 7, 07.2011, p. 699-705.

Research output: Contribution to journalArticle

Höglinger, GU, Melhem, NM, Dickson, DW, Sleiman, PMA, Wang, LS, Klei, L, Rademakers, R, De Silva, R, Litvan, I, Riley, DE, Van Swieten, JC, Heutink, P, Wszolek, ZK, Uitti, RJ, Vandrovcova, J, Hurtig, HI, Gross, RG, Maetzler, W, Goldwurm, S, Tolosa, E, Borroni, B, Pastor, P, Cantwell, LB, Han, MR, Dillman, A, Van Der Brug, MP, Gibbs, JR, Cookson, MR, Hernandez, DG, Singleton, AB, Farrer, MJ, Yu, CE, Golbe, LI, Revesz, T, Hardy, J, Lees, AJ, Devlin, B, Hakonarson, H, Müller, U, Schellenberg, GD, Albin, RL, Alonso, E, Antonini, A, Apfelbacher, M, Arnold, SE, Avila, J, Beach, TG, Beecher, S, Berg, D, Bird, TD, Bogdanovic, N, Boon, AJW, Bordelon, Y, Brice, A, Budka, H, Canesi, M, Chiu, WZ, Cilia, R, Colosimo, C, De Deyn, PP, De Yebenes, JG, Kaat, LD, Duara, R, Durr, A, Engelborghs, S, Fabbrini, G, Finch, NA, Flook, R, Frosch, MP, Gaig, C, Galasko, DR, Gasser, T, Gearing, M, Geller, ET, Ghetti, B, Graff-Radford, NR, Grossman, M, Hall, DA, Hazrati, LN, Höllerhage, M, Jankovic, J, Juncos, JL, Karydas, A, Kretzschmar, HA, Leber, I, Lee, VM, Lieberman, AP, Lyons, KE, Mariani, C, Masliah, E, Massey, LA, McLean, CA, Meucci, N, Miller, BL, Mollenhauer, B, Möller, JC, Morris, HR, Morris, C, O'Sullivan, SS, Oertel, WH, Ottaviani, D, Padovani, A, Pahwa, R, Pezzoli, G, Pickering-Brown, S, Poewe, W, Rabano, A, Rajput, A, Reich, SG, Respondek, G, Roeber, S, Rohrer, JD, Ross, OA, Rossor, MN, Sacilotto, G, Seeley, WW, Seppi, K, Silveira-Moriyama, L, Spina, S, Srulijes, K, St. George-Hyslop, P, Stamelou, M, Standaert, DG, Tesei, S, Tourtellotte, WW, Trenkwalder, C, Troakes, C, Trojanowski, JQ, Troncoso, JC, Van Deerlin, VM, Vonsattel, JPG, Wenning, GK, White, CL, Winter, P, Zarow, C & Zecchinelli, AL 2011, 'Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy', Nature Genetics, vol. 43, no. 7, pp. 699-705. https://doi.org/10.1038/ng.859
Höglinger GU, Melhem NM, Dickson DW, Sleiman PMA, Wang LS, Klei L et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nature Genetics. 2011 Jul;43(7):699-705. https://doi.org/10.1038/ng.859
Höglinger, Günter U. ; Melhem, Nadine M. ; Dickson, Dennis W. ; Sleiman, Patrick M A ; Wang, Li San ; Klei, Lambertus ; Rademakers, Rosa ; De Silva, Rohan ; Litvan, Irene ; Riley, David E. ; Van Swieten, John C. ; Heutink, Peter ; Wszolek, Zbigniew K. ; Uitti, Ryan J. ; Vandrovcova, Jana ; Hurtig, Howard I. ; Gross, Rachel G. ; Maetzler, Walter ; Goldwurm, Stefano ; Tolosa, Eduardo ; Borroni, Barbara ; Pastor, Pau ; Cantwell, Laura B. ; Han, Mi Ryung ; Dillman, Allissa ; Van Der Brug, Marcel P. ; Gibbs, J. Raphael ; Cookson, Mark R. ; Hernandez, Dena G. ; Singleton, Andrew B. ; Farrer, Matthew J. ; Yu, Chang En ; Golbe, Lawrence I. ; Revesz, Tamas ; Hardy, John ; Lees, Andrew J. ; Devlin, Bernie ; Hakonarson, Hakon ; Müller, Ulrich ; Schellenberg, Gerard D. ; Albin, Roger L. ; Alonso, Elena ; Antonini, Angelo ; Apfelbacher, Manuela ; Arnold, Steven E. ; Avila, Jesus ; Beach, Thomas G. ; Beecher, Sherry ; Berg, Daniela ; Bird, Thomas D. ; Bogdanovic, Nenad ; Boon, Agnita J W ; Bordelon, Yvette ; Brice, Alexis ; Budka, Herbert ; Canesi, Margherita ; Chiu, Wang Zheng ; Cilia, Roberto ; Colosimo, Carlo ; De Deyn, Peter P. ; De Yebenes, Justo Garcãa ; Kaat, Laura Donker ; Duara, Ranjan ; Durr, Alexandra ; Engelborghs, Sebastiaan ; Fabbrini, Giovanni ; Finch, Nicole A. ; Flook, Robyn ; Frosch, Matthew P. ; Gaig, Carles ; Galasko, Douglas R. ; Gasser, Thomas ; Gearing, Marla ; Geller, Evan T. ; Ghetti, Bernardino ; Graff-Radford, Neill R. ; Grossman, Murray ; Hall, Deborah A. ; Hazrati, Lili Naz ; Höllerhage, Matthias ; Jankovic, Joseph ; Juncos, Jorge L. ; Karydas, Anna ; Kretzschmar, Hans A. ; Leber, Isabelle ; Lee, Virginia M. ; Lieberman, Andrew P. ; Lyons, Kelly E. ; Mariani, Claudio ; Masliah, Eliezer ; Massey, Luke A. ; McLean, Catriona A. ; Meucci, Nicoletta ; Miller, Bruce L. ; Mollenhauer, Brit ; Möller, Jens C. ; Morris, Huw R. ; Morris, Chris ; O'Sullivan, Sean S. ; Oertel, Wolfgang H. ; Ottaviani, Donatella ; Padovani, Alessandro ; Pahwa, Rajesh ; Pezzoli, Gianni ; Pickering-Brown, Stuart ; Poewe, Werner ; Rabano, Alberto ; Rajput, Alex ; Reich, Stephen G. ; Respondek, Gesine ; Roeber, Sigrun ; Rohrer, Jonathan D. ; Ross, Owen A. ; Rossor, Martin N. ; Sacilotto, Giorgio ; Seeley, William W. ; Seppi, Klaus ; Silveira-Moriyama, Laura ; Spina, Salvatore ; Srulijes, Karin ; St. George-Hyslop, Peter ; Stamelou, Maria ; Standaert, David G. ; Tesei, Silvana ; Tourtellotte, Wallace W. ; Trenkwalder, Claudia ; Troakes, Claire ; Trojanowski, John Q. ; Troncoso, Juan C ; Van Deerlin, Vivianna M. ; Vonsattel, Jean Paul G ; Wenning, Gregor K. ; White, Charles L. ; Winter, Pia ; Zarow, Chris ; Zecchinelli, Anna L. / Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. In: Nature Genetics. 2011 ; Vol. 43, No. 7. pp. 699-705.
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title = "Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy",
abstract = "Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP (cases) and 3,247 controls (stage 1) followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals (P <5 × 10-8) associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component.",
author = "H{\"o}glinger, {G{\"u}nter U.} and Melhem, {Nadine M.} and Dickson, {Dennis W.} and Sleiman, {Patrick M A} and Wang, {Li San} and Lambertus Klei and Rosa Rademakers and {De Silva}, Rohan and Irene Litvan and Riley, {David E.} and {Van Swieten}, {John C.} and Peter Heutink and Wszolek, {Zbigniew K.} and Uitti, {Ryan J.} and Jana Vandrovcova and Hurtig, {Howard I.} and Gross, {Rachel G.} and Walter Maetzler and Stefano Goldwurm and Eduardo Tolosa and Barbara Borroni and Pau Pastor and Cantwell, {Laura B.} and Han, {Mi Ryung} and Allissa Dillman and {Van Der Brug}, {Marcel P.} and Gibbs, {J. Raphael} and Cookson, {Mark R.} and Hernandez, {Dena G.} and Singleton, {Andrew B.} and Farrer, {Matthew J.} and Yu, {Chang En} and Golbe, {Lawrence I.} and Tamas Revesz and John Hardy and Lees, {Andrew J.} and Bernie Devlin and Hakon Hakonarson and Ulrich M{\"u}ller and Schellenberg, {Gerard D.} and Albin, {Roger L.} and Elena Alonso and Angelo Antonini and Manuela Apfelbacher and Arnold, {Steven E.} and Jesus Avila and Beach, {Thomas G.} and Sherry Beecher and Daniela Berg and Bird, {Thomas D.} and Nenad Bogdanovic and Boon, {Agnita J W} and Yvette Bordelon and Alexis Brice and Herbert Budka and Margherita Canesi and Chiu, {Wang Zheng} and Roberto Cilia and Carlo Colosimo and {De Deyn}, {Peter P.} and {De Yebenes}, {Justo Garc{\~a}a} and Kaat, {Laura Donker} and Ranjan Duara and Alexandra Durr and Sebastiaan Engelborghs and Giovanni Fabbrini and Finch, {Nicole A.} and Robyn Flook and Frosch, {Matthew P.} and Carles Gaig and Galasko, {Douglas R.} and Thomas Gasser and Marla Gearing and Geller, {Evan T.} and Bernardino Ghetti and Graff-Radford, {Neill R.} and Murray Grossman and Hall, {Deborah A.} and Hazrati, {Lili Naz} and Matthias H{\"o}llerhage and Joseph Jankovic and Juncos, {Jorge L.} and Anna Karydas and Kretzschmar, {Hans A.} and Isabelle Leber and Lee, {Virginia M.} and Lieberman, {Andrew P.} and Lyons, {Kelly E.} and Claudio Mariani and Eliezer Masliah and Massey, {Luke A.} and McLean, {Catriona A.} and Nicoletta Meucci and Miller, {Bruce L.} and Brit Mollenhauer and M{\"o}ller, {Jens C.} and Morris, {Huw R.} and Chris Morris and O'Sullivan, {Sean S.} and Oertel, {Wolfgang H.} and Donatella Ottaviani and Alessandro Padovani and Rajesh Pahwa and Gianni Pezzoli and Stuart Pickering-Brown and Werner Poewe and Alberto Rabano and Alex Rajput and Reich, {Stephen G.} and Gesine Respondek and Sigrun Roeber and Rohrer, {Jonathan D.} and Ross, {Owen A.} and Rossor, {Martin N.} and Giorgio Sacilotto and Seeley, {William W.} and Klaus Seppi and Laura Silveira-Moriyama and Salvatore Spina and Karin Srulijes and {St. George-Hyslop}, Peter and Maria Stamelou and Standaert, {David G.} and Silvana Tesei and Tourtellotte, {Wallace W.} and Claudia Trenkwalder and Claire Troakes and Trojanowski, {John Q.} and Troncoso, {Juan C} and {Van Deerlin}, {Vivianna M.} and Vonsattel, {Jean Paul G} and Wenning, {Gregor K.} and White, {Charles L.} and Pia Winter and Chris Zarow and Zecchinelli, {Anna L.}",
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T1 - Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy

AU - Höglinger, Günter U.

AU - Melhem, Nadine M.

AU - Dickson, Dennis W.

AU - Sleiman, Patrick M A

AU - Wang, Li San

AU - Klei, Lambertus

AU - Rademakers, Rosa

AU - De Silva, Rohan

AU - Litvan, Irene

AU - Riley, David E.

AU - Van Swieten, John C.

AU - Heutink, Peter

AU - Wszolek, Zbigniew K.

AU - Uitti, Ryan J.

AU - Vandrovcova, Jana

AU - Hurtig, Howard I.

AU - Gross, Rachel G.

AU - Maetzler, Walter

AU - Goldwurm, Stefano

AU - Tolosa, Eduardo

AU - Borroni, Barbara

AU - Pastor, Pau

AU - Cantwell, Laura B.

AU - Han, Mi Ryung

AU - Dillman, Allissa

AU - Van Der Brug, Marcel P.

AU - Gibbs, J. Raphael

AU - Cookson, Mark R.

AU - Hernandez, Dena G.

AU - Singleton, Andrew B.

AU - Farrer, Matthew J.

AU - Yu, Chang En

AU - Golbe, Lawrence I.

AU - Revesz, Tamas

AU - Hardy, John

AU - Lees, Andrew J.

AU - Devlin, Bernie

AU - Hakonarson, Hakon

AU - Müller, Ulrich

AU - Schellenberg, Gerard D.

AU - Albin, Roger L.

AU - Alonso, Elena

AU - Antonini, Angelo

AU - Apfelbacher, Manuela

AU - Arnold, Steven E.

AU - Avila, Jesus

AU - Beach, Thomas G.

AU - Beecher, Sherry

AU - Berg, Daniela

AU - Bird, Thomas D.

AU - Bogdanovic, Nenad

AU - Boon, Agnita J W

AU - Bordelon, Yvette

AU - Brice, Alexis

AU - Budka, Herbert

AU - Canesi, Margherita

AU - Chiu, Wang Zheng

AU - Cilia, Roberto

AU - Colosimo, Carlo

AU - De Deyn, Peter P.

AU - De Yebenes, Justo Garcãa

AU - Kaat, Laura Donker

AU - Duara, Ranjan

AU - Durr, Alexandra

AU - Engelborghs, Sebastiaan

AU - Fabbrini, Giovanni

AU - Finch, Nicole A.

AU - Flook, Robyn

AU - Frosch, Matthew P.

AU - Gaig, Carles

AU - Galasko, Douglas R.

AU - Gasser, Thomas

AU - Gearing, Marla

AU - Geller, Evan T.

AU - Ghetti, Bernardino

AU - Graff-Radford, Neill R.

AU - Grossman, Murray

AU - Hall, Deborah A.

AU - Hazrati, Lili Naz

AU - Höllerhage, Matthias

AU - Jankovic, Joseph

AU - Juncos, Jorge L.

AU - Karydas, Anna

AU - Kretzschmar, Hans A.

AU - Leber, Isabelle

AU - Lee, Virginia M.

AU - Lieberman, Andrew P.

AU - Lyons, Kelly E.

AU - Mariani, Claudio

AU - Masliah, Eliezer

AU - Massey, Luke A.

AU - McLean, Catriona A.

AU - Meucci, Nicoletta

AU - Miller, Bruce L.

AU - Mollenhauer, Brit

AU - Möller, Jens C.

AU - Morris, Huw R.

AU - Morris, Chris

AU - O'Sullivan, Sean S.

AU - Oertel, Wolfgang H.

AU - Ottaviani, Donatella

AU - Padovani, Alessandro

AU - Pahwa, Rajesh

AU - Pezzoli, Gianni

AU - Pickering-Brown, Stuart

AU - Poewe, Werner

AU - Rabano, Alberto

AU - Rajput, Alex

AU - Reich, Stephen G.

AU - Respondek, Gesine

AU - Roeber, Sigrun

AU - Rohrer, Jonathan D.

AU - Ross, Owen A.

AU - Rossor, Martin N.

AU - Sacilotto, Giorgio

AU - Seeley, William W.

AU - Seppi, Klaus

AU - Silveira-Moriyama, Laura

AU - Spina, Salvatore

AU - Srulijes, Karin

AU - St. George-Hyslop, Peter

AU - Stamelou, Maria

AU - Standaert, David G.

AU - Tesei, Silvana

AU - Tourtellotte, Wallace W.

AU - Trenkwalder, Claudia

AU - Troakes, Claire

AU - Trojanowski, John Q.

AU - Troncoso, Juan C

AU - Van Deerlin, Vivianna M.

AU - Vonsattel, Jean Paul G

AU - Wenning, Gregor K.

AU - White, Charles L.

AU - Winter, Pia

AU - Zarow, Chris

AU - Zecchinelli, Anna L.

PY - 2011/7

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N2 - Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP (cases) and 3,247 controls (stage 1) followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals (P <5 × 10-8) associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component.

AB - Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP (cases) and 3,247 controls (stage 1) followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals (P <5 × 10-8) associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component.

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