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

Research output: Contribution to journalArticle

  • External authors:
  • 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
  • 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
  • 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

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. © 2011 Nature America, Inc. All rights reserved.

Bibliographical metadata

Original languageEnglish
Pages (from-to)699-705
Number of pages6
JournalNature Genetics
Volume43
Issue number7
DOIs
Publication statusPublished - Jul 2011