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

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Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease. / Theuns, J.; Verstraeten, A.; Sleegers, K.; Wauters, E.; Gijselinck, I.; Smolders, S.; Crosiers, D.; Corsmit, E.; Elinck, E.; Sharma, M.; Kruger, R.; Lesage, S.; Brice, A.; Chung, S. J.; Kim, M. J.; Kim, Y. J.; Ross, O. A.; Wszolek, Z. K.; Rogaeva, E.; Xi, Z.; Lang, A. E.; Klein, C.; Weissbach, A.; Mellick, G. D.; Silburn, P. A.; Hadjigeorgiou, G. M.; Dardiotis, E.; Hattori, N.; Ogaki, K.; Tan, E. K.; Zhao, Y.; Aasly, J.; Valente, E. M.; Petrucci, S.; Annesi, G.; Quattrone, A.; Ferrarese, C.; Brighina, L.; Deutschlander, A.; Puschmann, Andreas; Nilsson, C.; Garraux, G.; LeDoux, M. S.; Pfeiffer, R. F.; Boczarska-Jedynak, M.; Opala, G.; Maraganore, D. M.; Engelborghs, S.; De Deyn, P. P.; Cras, P.; Cruts, M.; Van Broeckhoven, C.

In: Neurology, Vol. 83, No. 21, 2014, p. 1906-13.

Research output: Contribution to journalArticle

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Theuns, J, Verstraeten, A, Sleegers, K, Wauters, E, Gijselinck, I, Smolders, S, Crosiers, D, Corsmit, E, Elinck, E, Sharma, M, Kruger, R, Lesage, S, Brice, A, Chung, SJ, Kim, MJ, Kim, YJ, Ross, OA, Wszolek, ZK, Rogaeva, E, Xi, Z, Lang, AE, Klein, C, Weissbach, A, Mellick, GD, Silburn, PA, Hadjigeorgiou, GM, Dardiotis, E, Hattori, N, Ogaki, K, Tan, EK, Zhao, Y, Aasly, J, Valente, EM, Petrucci, S, Annesi, G, Quattrone, A, Ferrarese, C, Brighina, L, Deutschlander, A, Puschmann, A, Nilsson, C, Garraux, G, LeDoux, MS, Pfeiffer, RF, Boczarska-Jedynak, M, Opala, G, Maraganore, DM, Engelborghs, S, De Deyn, PP, Cras, P, Cruts, M & Van Broeckhoven, C 2014, 'Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease', Neurology, vol. 83, no. 21, pp. 1906-13. https://doi.org/10.1212/wnl.0000000000001012

APA

Theuns, J., Verstraeten, A., Sleegers, K., Wauters, E., Gijselinck, I., Smolders, S., Crosiers, D., Corsmit, E., Elinck, E., Sharma, M., Kruger, R., Lesage, S., Brice, A., Chung, S. J., Kim, M. J., Kim, Y. J., Ross, O. A., Wszolek, Z. K., Rogaeva, E., ... Van Broeckhoven, C. (2014). Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease. Neurology, 83(21), 1906-13. https://doi.org/10.1212/wnl.0000000000001012

CBE

Theuns J, Verstraeten A, Sleegers K, Wauters E, Gijselinck I, Smolders S, Crosiers D, Corsmit E, Elinck E, Sharma M, Kruger R, Lesage S, Brice A, Chung SJ, Kim MJ, Kim YJ, Ross OA, Wszolek ZK, Rogaeva E, Xi Z, Lang AE, Klein C, Weissbach A, Mellick GD, Silburn PA, Hadjigeorgiou GM, Dardiotis E, Hattori N, Ogaki K, Tan EK, Zhao Y, Aasly J, Valente EM, Petrucci S, Annesi G, Quattrone A, Ferrarese C, Brighina L, Deutschlander A, Puschmann A, Nilsson C, Garraux G, LeDoux MS, Pfeiffer RF, Boczarska-Jedynak M, Opala G, Maraganore DM, Engelborghs S, De Deyn PP, Cras P, Cruts M, Van Broeckhoven C. 2014. Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease. Neurology. 83(21):1906-13. https://doi.org/10.1212/wnl.0000000000001012

MLA

Vancouver

Theuns J, Verstraeten A, Sleegers K, Wauters E, Gijselinck I, Smolders S et al. Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease. Neurology. 2014;83(21):1906-13. https://doi.org/10.1212/wnl.0000000000001012

Author

Theuns, J. ; Verstraeten, A. ; Sleegers, K. ; Wauters, E. ; Gijselinck, I. ; Smolders, S. ; Crosiers, D. ; Corsmit, E. ; Elinck, E. ; Sharma, M. ; Kruger, R. ; Lesage, S. ; Brice, A. ; Chung, S. J. ; Kim, M. J. ; Kim, Y. J. ; Ross, O. A. ; Wszolek, Z. K. ; Rogaeva, E. ; Xi, Z. ; Lang, A. E. ; Klein, C. ; Weissbach, A. ; Mellick, G. D. ; Silburn, P. A. ; Hadjigeorgiou, G. M. ; Dardiotis, E. ; Hattori, N. ; Ogaki, K. ; Tan, E. K. ; Zhao, Y. ; Aasly, J. ; Valente, E. M. ; Petrucci, S. ; Annesi, G. ; Quattrone, A. ; Ferrarese, C. ; Brighina, L. ; Deutschlander, A. ; Puschmann, Andreas ; Nilsson, C. ; Garraux, G. ; LeDoux, M. S. ; Pfeiffer, R. F. ; Boczarska-Jedynak, M. ; Opala, G. ; Maraganore, D. M. ; Engelborghs, S. ; De Deyn, P. P. ; Cras, P. ; Cruts, M. ; Van Broeckhoven, C. / Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease. In: Neurology. 2014 ; Vol. 83, No. 21. pp. 1906-13.

RIS

TY - JOUR

T1 - Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease

AU - Theuns, J.

AU - Verstraeten, A.

AU - Sleegers, K.

AU - Wauters, E.

AU - Gijselinck, I.

AU - Smolders, S.

AU - Crosiers, D.

AU - Corsmit, E.

AU - Elinck, E.

AU - Sharma, M.

AU - Kruger, R.

AU - Lesage, S.

AU - Brice, A.

AU - Chung, S. J.

AU - Kim, M. J.

AU - Kim, Y. J.

AU - Ross, O. A.

AU - Wszolek, Z. K.

AU - Rogaeva, E.

AU - Xi, Z.

AU - Lang, A. E.

AU - Klein, C.

AU - Weissbach, A.

AU - Mellick, G. D.

AU - Silburn, P. A.

AU - Hadjigeorgiou, G. M.

AU - Dardiotis, E.

AU - Hattori, N.

AU - Ogaki, K.

AU - Tan, E. K.

AU - Zhao, Y.

AU - Aasly, J.

AU - Valente, E. M.

AU - Petrucci, S.

AU - Annesi, G.

AU - Quattrone, A.

AU - Ferrarese, C.

AU - Brighina, L.

AU - Deutschlander, A.

AU - Puschmann, Andreas

AU - Nilsson, C.

AU - Garraux, G.

AU - LeDoux, M. S.

AU - Pfeiffer, R. F.

AU - Boczarska-Jedynak, M.

AU - Opala, G.

AU - Maraganore, D. M.

AU - Engelborghs, S.

AU - De Deyn, P. P.

AU - Cras, P.

AU - Cruts, M.

AU - Van Broeckhoven, C.

N1 - 21

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Cohort Studies

KW - DNA Repeat Expansion/ genetics

KW - Female

KW - Humans

KW - Internationality

KW - Male

KW - Middle Aged

KW - Parkinson Disease/ diagnosis/epidemiology/ genetics

KW - Proteins/ genetics

U2 - 10.1212/wnl.0000000000001012

DO - 10.1212/wnl.0000000000001012

M3 - Article

VL - 83

SP - 1906

EP - 1913

JO - Neurology

JF - Neurology

SN - 1526-632X

IS - 21

ER -