Unknown

Dataset Information

0

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.

SUBMITTER: Hoglinger GU 

PROVIDER: S-EPMC3125476 | biostudies-other | 2011 Jun

REPOSITORIES: biostudies-other

Json Xml
altmetric image

Publications

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

Höglinger Günter U GU   Melhem Nadine M NM   Dickson Dennis W DW   Sleiman Patrick M A PM   Wang Li-San LS   Klei Lambertus L   Rademakers Rosa R   de Silva Rohan R   Litvan Irene I   Riley David E DE   van Swieten John C JC   Heutink Peter P   Wszolek Zbigniew K ZK   Uitti Ryan J RJ   Vandrovcova Jana J   Hurtig Howard I HI   Gross Rachel G RG   Maetzler Walter W   Goldwurm Stefano S   Tolosa Eduardo E   Borroni Barbara B   Pastor Pau P   Cantwell Laura B LB   Han Mi Ryung MR   Dillman Allissa A   van der Brug Marcel P MP   Gibbs J Raphael JR   Cookson Mark R MR   Hernandez Dena G DG   Singleton Andrew B AB   Farrer Matthew J MJ   Yu Chang-En CE   Golbe Lawrence I LI   Revesz Tamas T   Hardy John J   Lees Andrew J AJ   Devlin Bernie B   Hakonarson Hakon H   Müller Ulrich U   Schellenberg Gerard D GD  

Nature genetics 20110619 7

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) follo  ...[more]