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

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 XiAnthony 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

    Research output: Contribution to journalArticlepeer-review

    48 Citations (Scopus)


    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.

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

    Bibliographical note

    © 2014 American Academy of Neurology.


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


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