Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease

Research output: Contribution to journalArticle


OBJECTIVES: The objective of this study is to clarify the role of (G4C2)n expansions in the etiology of Parkinson disease (PD) in the worldwide multicenter Genetic Epidemiology of Parkinson's Disease (GEO-PD) cohort. METHODS: C9orf72 (G4C2)n repeats were assessed in a GEO-PD cohort of 7,494 patients diagnosed with PD and 5,886 neurologically healthy control individuals ascertained in Europe, Asia, North America, and Australia. RESULTS: A pathogenic (G4C2)n>60 expansion was detected in only 4 patients with PD (4/7,232; 0.055%), all with a positive family history of neurodegenerative dementia, amyotrophic lateral sclerosis, or atypical parkinsonism, while no carriers were detected with typical sporadic or familial PD. Meta-analysis revealed a small increase in risk of PD with an increasing number of (G4C2)n repeats; however, we could not detect a robust association between the C9orf72 (G4C2)n repeat and PD, and the population attributable risk was low. CONCLUSIONS: Together, these findings indicate that expansions in C9orf72 do not have a major role in the pathogenesis of PD. Testing for C9orf72 repeat expansions should only be considered in patients with PD who have overt symptoms of frontotemporal lobar degeneration/amyotrophic lateral sclerosis or apparent family history of neurodegenerative dementia or motor neuron disease.


  • J. Theuns
  • A. Verstraeten
  • K. Sleegers
  • E. Wauters
  • I. Gijselinck
  • S. Smolders
  • D. Crosiers
  • E. Corsmit
  • E. Elinck
  • M. Sharma
  • R. Kruger
  • S. Lesage
  • A. Brice
  • S. J. Chung
  • M. J. Kim
  • Y. J. Kim
  • O. A. Ross
  • Z. K. Wszolek
  • E. Rogaeva
  • Z. Xi
  • A. E. Lang
  • C. Klein
  • A. Weissbach
  • G. D. Mellick
  • P. A. Silburn
  • G. M. Hadjigeorgiou
  • E. Dardiotis
  • N. Hattori
  • K. Ogaki
  • E. K. Tan
  • Y. Zhao
  • J. Aasly
  • E. M. Valente
  • S. Petrucci
  • G. Annesi
  • A. Quattrone
  • C. Ferrarese
  • L. Brighina
  • A. Deutschlander
  • C. Nilsson
  • G. Garraux
  • M. S. LeDoux
  • R. F. Pfeiffer
  • M. Boczarska-Jedynak
  • G. Opala
  • D. M. Maraganore
  • S. Engelborghs
  • P. P. De Deyn
  • P. Cras
  • M. Cruts
  • C. Van Broeckhoven
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology


  • Cohort Studies, DNA Repeat Expansion/ genetics, Female, Humans, Internationality, Male, Middle Aged, Parkinson Disease/ diagnosis/epidemiology/ genetics, Proteins/ genetics
Original languageEnglish
Pages (from-to)1906-13
Issue number21
Publication statusPublished - 2014
Publication categoryResearch

Bibliographic note


Total downloads

No data available