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

Research output: Contribution to journalArticle


  • Jessie Theuns
  • Aline Verstraeten
  • Kristel Sleegers
  • Eline Wauters
  • Ilse Gijselinck
  • Stefanie Smolders
  • David Crosiers
  • Ellen Corsmit
  • Ellen Elinck
  • Manu Sharma
  • Rejko Krüger
  • Suzanne Lesage
  • Alexis Brice
  • Sun Ju Chung
  • Mi-Jung Kim
  • Young Jin Kim
  • Owen A Ross
  • Zbigniew K Wszolek
  • Ekaterina Rogaeva
  • Zhengrui Xi
  • Anthony E Lang
  • Christine Klein
  • Anne Weissbach
  • George D Mellick
  • Peter A Silburn
  • Georgios M Hadjigeorgiou
  • Efthimios Dardiotis
  • Nobutaka Hattori
  • Kotaro Ogaki
  • Eng-King Tan
  • Yi Zhao
  • Jan Aasly
  • Enza Maria Valente
  • Simona Petrucci
  • Grazia Annesi
  • Aldo Quattrone
  • Carlo Ferrarese
  • Laura Brighina
  • Angela Deutschländer
  • Andreas Puschmann
  • Christer Nilsson
  • Gaëtan Garraux
  • Mark S LeDoux
  • Ronald F Pfeiffer
  • Magdalena Boczarska-Jedynak
  • Grzegorz Opala
  • Demetrius M Maraganore
  • Sebastiaan Engelborghs
  • Peter Paul De Deyn
  • Genetic Epidemiology Of Parkinson's Disease (GEO-PD) Consortium
  • Karen Morrison


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.

Bibliographic note

© 2014 American Academy of Neurology.


Original languageEnglish
Pages (from-to)1906-13
Number of pages8
Issue number21
Publication statusPublished - 18 Nov 2014


  • Cohort Studies, DNA Repeat Expansion, Female, Humans, Internationality, Male, Middle Aged, Parkinson Disease, Proteins