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.
authors.affiliation: Department of Neurology, Philipps-Universität, Marburg, Germany.
authors.forename: Günter U
authors.initials: GU
authors.lastname: Höglinger
authors.forename: Nadine M
authors.initials: NM
authors.lastname: Melhem
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Patrick M A
authors.initials: PM
authors.lastname: Sleiman
authors.forename: Li-San
authors.initials: LS
authors.lastname: Wang
authors.forename: Lambertus
authors.initials: L
authors.lastname: Klei
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.forename: Rohan
authors.initials: R
authors.lastname: de Silva
authors.forename: Irene
authors.initials: I
authors.lastname: Litvan
authors.forename: David E
authors.initials: DE
authors.lastname: Riley
authors.forename: John C
authors.initials: JC
authors.lastname: van Swieten
authors.forename: Peter
authors.initials: P
authors.lastname: Heutink
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Uitti
authors.forename: Jana
authors.initials: J
authors.lastname: Vandrovcova
authors.forename: Howard I
authors.initials: HI
authors.lastname: Hurtig
authors.forename: Rachel G
authors.initials: RG
authors.lastname: Gross
authors.forename: Walter
authors.initials: W
authors.lastname: Maetzler
authors.forename: Stefano
authors.initials: S
authors.lastname: Goldwurm
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
authors.forename: Pau
authors.initials: P
authors.lastname: Pastor
authors.forename: Laura B
authors.initials: LB
authors.lastname: Cantwell
authors.forename: Mi Ryung
authors.initials: MR
authors.lastname: Han
authors.forename: Allissa
authors.initials: A
authors.lastname: Dillman
authors.forename: Marcel P
authors.initials: MP
authors.lastname: van der Brug
authors.forename: J Raphael
authors.initials: JR
authors.lastname: Gibbs
authors.forename: Mark R
authors.initials: MR
authors.lastname: Cookson
authors.forename: Dena G
authors.initials: DG
authors.lastname: Hernandez
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: Chang-En
authors.initials: CE
authors.lastname: Yu
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Golbe
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lees
authors.forename: Bernie
authors.initials: B
authors.lastname: Devlin
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Ulrich
authors.initials: U
authors.lastname: Müller
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Schellenberg
mesh_terms: D016022:Case-Control Studies; D002877:Chromosomes, Human / Q000235:genetics; D015331:Cohort Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D012307:Risk Factors; D013494:Supranuclear Palsy, Progressive / Q000235:genetics* / Q000473:pathology; D024801:Tauopathies / Q000235:genetics* / Q000473:pathology; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins