1. Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease
- Author
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Theuns, Jessie, Verstraeten, Aline, Krüger, Rejko, Puschmann, Andrea, Ritz, Beate, Rogaeva, Ekaterina, Sazci, Ali, Slawek, Jaroslaw, Stefanis, Leonidas, Tan, Eng-King, Toda, Tatsushi, Toft, Matthias, Van Broeckhoven, Christine, Lesage, Suzanne, Wirdefeldt, Karin, Woitalla, Dirk, Wszolek, Zbigniew K, Zimprich, Alexander, Brice, Alexis, Chung, Sun Ju, Kim, Mi-Jung, Kim, Young Jin, Ross, Owen A, Xi, Zhengrui, Sleegers, Kristel, Lang, Anthony E, Klein, Christine, Weissbach, Anne, Mellick, George D, Silburn, Peter A, Hadjigeorgiou, Georgios M, Dardiotis, Efthimios, Hattori, Nobutaka, Ogaki, Kotaro, Wauters, Eline, Zhao, Yi, Aasly, Jan, Valente, Enza Maria, Petrucci, Simona, Annesi, Grazia, Quattrone, Aldo, Ferrarese, Carlo, Brighina, Laura, Deutschländer, Angela, Puschmann, Andreas, Gijselinck, Ilse, Nilsson, Christer, Garraux, Gaëtan, LeDoux, Mark S, Pfeiffer, Ronald F, Boczarska-Jedynak, Magdalena, Opala, Grzegorz, Maraganore, Demetrius M, Engelborghs, Sebastiaan, De Deyn, Peter Paul, Cras, Patrick, Smolders, Stefanie, Cruts, Marc, Consortium, GEO-PD, Farrer, Matthew J, Aasly, Jan O, Elbaz, Alexis, Ioannidis, John P, Annesi, Grazie, Crosiers, David, Bozi, Maria, Curie, Marie, Carmine-Belin, Andrea, Carr, Jonathan, Carroll, Camille, Chen, Sheng-Di, Cosentino, Carlos, Cresswell, Silke, Corsmit, Ellen, Deutschlaender, Angela, Foroud, Tatiana, Goldwurm, Stefano, Hadjigeorgiou, George, Chartier-Harlin, Marie-Christine, Hassan, Anhar, Hentati, Faycal, Elinck, Ellen, Jeon, Beom Seok, Kawakami, Hideshi, Kim, Yun Joong, Kishore, Asha, Koks, Sulev, Krainc, Dimitri, Krygowska-Wajs, Anna, Lin, Juei-Jueng, Lynch, Tim, Sharma, Manu, Mellick, George, Morrison, Karen E, Munhoz, Renato P, Pastor, Pao, Payami, Haydeh, Pchelina, Sofya N, Petersburg, Saint, Petersen, Maria Skaalum, Theuns, J, Verstraeten, A, Sleegers, K, Wauters, E, Gijselinck, I, Smolders, S, Crosiers, D, Corsmit, E, Elinck, E, Sharma, M, Krüger, R, Lesage, S, Brice, A, Chung, S, Kim, M, Kim, Y, Ross, O, Wszolek, Z, Rogaeva, E, Xi, Z, Lang, A, Klein, C, Weissbach, A, Mellick, G, Silburn, P, Hadjigeorgiou, G, Dardiotis, E, Hattori, N, Ogaki, K, Tan, E, Zhao, Y, Aasly, J, Valente, E, Petrucci, S, Annesi, G, Quattrone, A, Ferrarese, C, Brighina, L, Deutschländer, A, Puschmann, A, Nilsson, C, Garraux, G, Ledoux, M, Pfeiffer, R, Boczarska Jedynak, M, Opala, G, Maraganore, D, Engelborghs, S, De Deyn, P, Cras, P, Cruts, M, Van Broeckhoven, C, Clinical sciences, Neurology, Physiotherapy, Human Physiology and Anatomy, and Pathologic Biochemistry and Physiology
- Subjects
Male ,Pathology ,Parkinson's disease ,Internationality ,Gastroenterology ,Cohort Studies ,0302 clinical medicine ,C9orf72 ,genetics [Parkinson Disease] ,dna repeat expansion ,Amyotrophic lateral sclerosis ,Family history ,Parkinson Disease/ diagnosis/epidemiology/ genetics ,Proteins/ genetics ,Medicine(all) ,0303 health sciences ,Frontotemporal lobar degeneration ,Middle Aged ,3. Good health ,c9orf72 protein ,cohort studies ,female ,humans ,internationality ,male ,middle aged ,parkinson disease ,proteins ,Neurology ,repeat-primed ,Proteins/genetics ,Cohort studies ,Female ,epidemiology [Parkinson Disease] ,diagnosis [Parkinson Disease] ,medicine.medical_specialty ,short tandem repeat ,genetics [DNA Repeat Expansion] ,Article ,DNA Repeat Expansion/genetics ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,ddc:610 ,030304 developmental biology ,DNA Repeat Expansion/ genetics ,C9orf72 Protein ,business.industry ,Parkinson Disease/diagnosis ,Proteins ,medicine.disease ,genetics [Proteins] ,Genetic epidemiology ,Genetic Epidemiology of Parkinson's Disease ,Attributable risk ,Etiology ,Human medicine ,Neurology (clinical) ,C9orf72 protein, human ,business ,030217 neurology & neurosurgery - Abstract
Objectives: The objective of this study is to clarify the role of (G 4 C 2 ) n expansions in the etiology of Parkinson disease (PD) in the worldwide multicenter Genetic Epidemiology of Parkinson9s Disease (GEO-PD) cohort. Methods: C9orf72 (G 4 C 2 ) 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 (G 4 C 2 ) 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 (G 4 C 2 ) n repeats; however, we could not detect a robust association between the C9orf72 (G 4 C 2 ) 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.
- Published
- 2014
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