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

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title = "Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease",
abstract = "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.",
keywords = "Cohort Studies, DNA Repeat Expansion/ genetics, Female, Humans, Internationality, Male, Middle Aged, Parkinson Disease/ diagnosis/epidemiology/ genetics, Proteins/ genetics",
author = "J. Theuns and A. Verstraeten and K. Sleegers and E. Wauters and I. Gijselinck and S. Smolders and D. Crosiers and E. Corsmit and E. Elinck and M. Sharma and R. Kruger and S. Lesage and A. Brice and Chung, {S. J.} and Kim, {M. J.} and Kim, {Y. J.} and Ross, {O. A.} and Wszolek, {Z. K.} and E. Rogaeva and Z. Xi and Lang, {A. E.} and C. Klein and A. Weissbach and Mellick, {G. D.} and Silburn, {P. A.} and Hadjigeorgiou, {G. M.} and E. Dardiotis and N. Hattori and K. Ogaki and Tan, {E. K.} and Y. Zhao and J. Aasly and Valente, {E. M.} and S. Petrucci and G. Annesi and A. Quattrone and C. Ferrarese and L. Brighina and A. Deutschlander and Andreas Puschmann and C. Nilsson and G. Garraux and LeDoux, {M. S.} and Pfeiffer, {R. F.} and M. Boczarska-Jedynak and G. Opala and Maraganore, {D. M.} and S. Engelborghs and {De Deyn}, {P. P.} and P. Cras and M. Cruts and {Van Broeckhoven}, C.",
note = "21",
year = "2014",
doi = "10.1212/wnl.0000000000001012",
language = "English",
volume = "83",
pages = "1906--13",
journal = "Neurology",
issn = "1526-632X",
publisher = "American Academy of Neurology",
number = "21",