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

PSP Genetics Study Group

Research output: Contribution to journalArticlepeer-review

453 Citations (Scopus)

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
Pages (from-to)699-705
Number of pages7
JournalNature Genetics
Volume43
Issue number7
DOIs
Publication statusPublished - 19 Jun 2011
Externally publishedYes

Keywords

  • Case-Control Studies
  • Chromosomes, Human/genetics
  • Cohort Studies
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome-Wide Association Study
  • Humans
  • Polymorphism, Single Nucleotide/genetics
  • Prognosis
  • Risk Factors
  • Supranuclear Palsy, Progressive/genetics
  • Tauopathies/genetics
  • tau Proteins/genetics

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