SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson's Disease
Por:
Martín-Flores, N, Antonelli, F, Cerquera, C, Moreno, V, Manduchi, E, Moore, JH, Noyce, AJ, Kaiyrzhanov, R, Middlehurst, B, Kia, DA, Tan, M, Houlden, H, Morris, HR, Plun-Favreau, H, Holmans, P, Hardy, J, Trabzuni, D, Bras, J, Quinn, J, Mok, KY, Kinghorn, KJ, Billingsley, K, Wood, NW, Lewis, P, Schreglmann, S, Guerreiro, R, Lovering, R, R'Bibo, L, Manzoni, C, Rizig, M, Ryten, M, Guelfi, S, Escott-Price, V, Chelban, V, Foltynie, T, Williams, N, Morrison, KE, Clarke, C, Brice, A, Danjou, F, Lesage, S, Corvol, JC, Martinez, M, Schulte, C, Brockmann, K, Simóon-Sáanchez, J, Heutink, P, Rizzu, P, Sharma, M, Gasser, T, Nicolas, A, Cookson, MR, Bandres-Ciga, S, Blauwendraat, C, Craig, DW, Faghri, F, Gibbs, JR, Hernandez, DG, Van Keuren-Jensen, K, Shulman, JM, Iwaki, H, Leonard, HL, Nalls, MA, Robak, L, Lubbe, S, Finkbeiner, S, Mencacci, NE, Lungu, C, Singleton, AB, Scholz, SW, Reed, X, Alcalay, RN, Gan-Or, Z, Rouleau, GA, Krohn, L, van Hilten, JJ, Marinus, J, Adarmes-Góomez, AD, Aguilar, I, Alvarez, I, Alvarez, V, Barrero, FJ, Yarza, JAB, Bernal-Bernal, I, Blazquez, M, Bonilla-Toribio, M, Botía, JA, Boungiorno, MT, Buiza-Rueda, D, Cámara, A, Carrillo, F, Carrión-Claro, M, Cerdan, D, Clarimón, J, Compta, Y, de la Casa, B, Diez-Fairen, M, Dols-Icardo, O, Duarte, J, Duran, R, Escamilla-Sevilla, F, Feliz, C, Fernández, M, Fernández-Santiago, R, Garcia, C, García-Ruiz, P, Gómez-Garre, P, Heredia, MJG, Gonzalez-Aramburu, I, Pagola, AG, Hoenicka J, Infante, J, Jesús, S, Jimenez-Escrig, A, Kulisevsky, J, Labrador-Espinosa, MA, Lopez-Sendon, JL, Arregui, ALD, Macias, D, Torres, IM, Marín, J, Marti, MJ, Martínez-Castrillo, C, Méndez-del-Barrio, C, González, MM, Mata, M, Mínguez, A, Mir, P, Rezola, EM, Muñoz, E, Pagonabarraga, J, Pascual-Sedano, B, Pastor, P, Errazquin, FP, Perinán-Tocino, T, Ruiz-Martínez, J, Ruz, C, Rodriguez, AS, Sierra, M, Suarez-Sanmartin, E, Tabernero, C, Tartari, JP, Tejera-Parrado, C, Tolosa, E, Valldeoriola, F, Vargas-González, L, Vela, L, Vives, F, Zimprich, A, Pihlstrom, L, Toft, M, Koks, S, Taba, P, Hassin-Baer, S, Martí, MJ, Ezquerra, M and Malagelada, C
Publicada:
1 sep 2019
Resumen:
Background Single nucleotide polymorphisms (SNPs) in the alpha-synuclein (SNCA) gene are associated with differential risk and age at onset (AAO) of both idiopathic and Leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson's disease (PD). Yet potential combinatory or synergistic effects among several modulatory SNPs for PD risk or AAO remain largely underexplored. Objectives The mechanistic target of rapamycin (mTOR) signaling pathway is functionally impaired in PD. Here we explored whether SNPs in the mTOR pathway, alone or by epistatic interaction with known susceptibility factors, can modulate PD risk and AAO. Methods Based on functional relevance, we selected a total of 64 SNPs mapping to a total of 57 genes from the mTOR pathway and genotyped a discovery series cohort encompassing 898 PD patients and 921 controls. As a replication series, we screened 4170 PD and 3014 controls available from the International Parkinson's Disease Genomics Consortium. Results In the discovery series cohort, we found a 4-loci interaction involving STK11 rs8111699, FCHSD1 rs456998, GSK3B rs1732170, and SNCA rs356219, which was associated with an increased risk of PD (odds ratio = 2.59, P < .001). In addition, we also found a 3-loci epistatic combination of RPTOR rs11868112 and RPS6KA2 rs6456121 with SNCA rs356219, which was associated (odds ratio = 2.89; P < .0001) with differential AAO. The latter was further validated (odds ratio = 1.56; P = 0.046-0.047) in the International Parkinson's Disease Genomics Consortium cohort. Conclusions These findings indicate that genetic variability in the mTOR pathway contributes to SNCA effects in a nonlinear epistatic manner to modulate differential AAO in PD, unraveling the contribution of this cascade in the pathogenesis of the disease. (c) 2019 International Parkinson and Movement Disorder Society
Filiaciones:
Martín-Flores, N:
Univ Barcelona, Dept Biomed, Unit Biochem, Casanova 143,North Wing 3rd Floor, E-08036 Barcelona, Catalonia, Spain
Univ Barcelona, Inst Neurosci, Barcelona, Catalonia, Spain
Antonelli, F:
Hosp Clin Barcelona, Neurol Serv, Barcelona, Catalonia, Spain
Cerquera, C:
Hosp Clin Barcelona, Neurol Serv, Barcelona, Catalonia, Spain
Moreno, V:
Hosp Clin Barcelona, Neurol Serv, Barcelona, Catalonia, Spain
Manduchi, E:
Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA
Moore, JH:
Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA
Noyce, AJ:
QMUL, Wolfson Inst Prevent Med, Prevent Neurol Unit, London, England
UCL, Dept Mol Neurosci, London, England
Kaiyrzhanov, R:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
Middlehurst, B:
Univ Liverpool, Inst Translat Med, Liverpool, Merseyside, England
Kia, DA:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
UCL, Genet Inst, London, England
Tan, M:
UCL, Dept Clin Neurosci, London, England
Houlden, H:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
Morris, HR:
UCL, Dept Clin Neurosci, London, England
Plun-Favreau, H:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
Holmans, P:
MRC Ctr Neuropsychiat Genet & Genom, Biostat & Bioinformat Unit, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales
Hardy, J:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
Trabzuni, D:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia
Bras, J:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
UCL, UK Dementia Res Inst, London, England
Quinn, J:
Univ Liverpool, Inst Translat Med, Liverpool, Merseyside, England
Mok, KY:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
Kinghorn, KJ:
UCL, Inst Hlth Ageing, London, England
Billingsley, K:
Univ Liverpool, Inst Translat Med, Liverpool, Merseyside, England
Wood, NW:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
UCL, Genet Inst, London, England
Lewis, P:
Univ Reading, Reading, Berks, England
Schreglmann, S:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
Guerreiro, R:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
UCL, UK Dementia Res Inst, London, England
Lovering, R:
UCL, London, England
R'Bibo, L:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
Manzoni, C:
Univ Reading, Reading, Berks, England
Rizig, M:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
Ryten, M:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
Guelfi, S:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
Escott-Price, V:
Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Gen, Cardiff, S Glam, Wales
Chelban, V:
UCL, Dept Mol Neurosci, Inst Neurol, London, England
Foltynie, T:
UCL, Inst Neurol, London, England
Williams, N:
MRC Ctr Neuropsychiat Genet & Gen, Cardiff, S Glam, Wales
Morrison, KE:
Univ Southampton, Fac Med, Southampton, Hants, England
Clarke, C:
Univ Birmingham, Birmingham, W Midlands, England
Sandwell & West Birmingham Hosp NHS Trust, Birmingham, W Midlands, England
Brice, A:
UPMC Univ Paris 06, Sorbonne Univ, Pitie Salpetriere Hosp, AP HP,ICM,INSERM,CNRS,UMR 7225,U 1127,UMR S 1127, Paris, France
Danjou, F:
UPMC Univ Paris 06, Sorbonne Univ, Pitie Salpetriere Hosp, AP HP,ICM,INSERM,CNRS,UMR 7225,U 1127,UMR S 1127, Paris, France
Lesage, S:
UPMC Univ Paris 06, Sorbonne Univ, Pitie Salpetriere Hosp, AP HP,ICM,INSERM,CNRS,UMR 7225,U 1127,UMR S 1127, Paris, France
Corvol, JC:
UPMC Univ Paris 06, Ctr Invest Clin Pitie Neurosci CIC 1422, Pitie Salpetriere Hosp,UMR 7225,UMR S 1127,AP HP, Sorbonne Univ,ICM,INSERM,U 1127,CNRS,Inst Cerveau, Paris, France
Martinez, M:
INSERM, UMR 1220, Toulouse, France
Paul Sabatier Univ, Toulouse, France
Schulte, C:
Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany
German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany
Brockmann, K:
Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany
German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany
Simóon-Sáanchez, J:
Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany
German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany
Heutink, P:
Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany
German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany
Rizzu, P:
German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany
Sharma, M:
Univ Tubingen, Ctr Genet Epidemiol, Inst Clin Epidemiol & Appl Biometry, Tubingen, Germany
Gasser, T:
German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany
Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany
Nicolas, A:
NIA, Lab Neurogenet, Bethesda, MD 20892 USA
Cookson, MR:
NIA, Lab Neurogenet, Bethesda, MD 20892 USA
Bandres-Ciga, S:
NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA
Inst Invest Biosanitaria Granada Ibs GRANADA, Granada, Spain
NIA, Lab Neurogenet, Bethesda, MD 20892 USA
Blauwendraat, C:
NIA, Bethesda, MD 20892 USA
NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA
Craig, DW:
Univ Southern Calif, Keck Sch Med, Dept Translat Gen, Los Angeles, CA 90033 USA
Faghri, F:
NIA, Lab Neurogenet, Bethesda, MD 20892 USA
Univ Illinois, Dept Comp Sci, Urbana, IL USA
Gibbs, JR:
NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA
Hernandez, DG:
NIA, Lab Neurogenet, Bethesda, MD 20892 USA
Van Keuren-Jensen, K:
TGen, Neurogen Div, Phoenix, AZ USA
Shulman, JM:
Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA
Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA
Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA
Iwaki, H:
NIA, Lab Neurogenet, Bethesda, MD 20892 USA
Leonard, HL:
NIA, Lab Neurogenet, Bethesda, MD 20892 USA
Nalls, MA:
NIA, Lab Neurogenet, Bethesda, MD 20892 USA
CEO Consultant Data Tecn Int, Glen Echo, MD USA
Robak, L:
Baylor Coll Med, Houston, TX 77030 USA
Lubbe, S:
Northwestern Univ, Feinberg Sch Med, Ken & Ruth Davee Dept Neurol, Chicago, IL 60611 USA
Finkbeiner, S:
Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA
Univ Calif San Francisco, Dept Physiol, Box 0444, San Francisco, CA USA
Gladstone Inst Neurol Dis, San Francisco, CA USA
Taube Koret Ctr Neurodegenerat Dis Res, San Francisco, CA USA
Mencacci, NE:
Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA
Lungu, C:
NINDS, Div Clin Res, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA
Singleton, AB:
NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA
NIA, Lab Neurogenet, Bethesda, MD 20892 USA
Scholz, SW:
NINDS, Neurodegenerat Dis Res Unit, Bethesda, MD 20892 USA
Reed, X:
NIA, Lab Neurogenet, Bethesda, MD 20892 USA
Alcalay, RN:
Columbia Univ, Coll Phys & Surg, Med Ctr, Dept Neurol, New York, NY USA
Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, Coll Phys & Surg, New York, NY USA
Gan-Or, Z:
McGill Univ, Montreal Neurol Inst & Hosp, Dept Neurol & Neurosurg, Dept Human Genet, Montreal, PQ H3A 0G4, Canada
Rouleau, GA:
McGill Univ, Montreal Neurol Inst & Hosp, Dept Neurol & Neurosurg, Dept Human Genet, Montreal, PQ H3A 0G4, Canada
Krohn, L:
McGill Univ, Montreal Neurol Inst & Hosp, Dept Neurol & Neurosurg, Dept Human Genet, Montreal, PQ H3A 0G4, Canada
van Hilten, JJ:
Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands
Marinus, J:
Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands
Adarmes-Góomez, AD:
Univ Seville, Hosp Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain
Aguilar, I:
Univ Hosp Mutua Terrassa, Fundacio Docencia & Recerca Mutua Terrassa, Barcelona, Spain
Univ Hosp Mutua Terrassa, Movement Disorders Unit, Dept Neurol, Barcelona, Spain
Alvarez, I:
Univ Hosp Mutua Terrassa, Fundacio Docencia & Recerca Mutua Terrassa, Barcelona, Spain
Univ Hosp Mutua Terrassa, Movement Disorders Unit, Dept Neurol, Barcelona, Spain
Alvarez, V:
Hosp Univ Cent Asturias, Oviedo, Spain
Barrero, FJ:
Univ Granada, Hosp Univ San Cecilio Granada, Granada, Spain
Yarza, JAB:
Inst Invest Sanitaria Biodonostia, San Sebastian, Spain
Bernal-Bernal, I:
Univ Seville, Hosp Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain
Blazquez, M:
Hosp Univ Cent Asturias, Oviedo, Spain
Bonilla-Toribio, M:
Univ Seville, Hosp Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain
Botía, JA:
Univ Murcia, Murcia, Spain
Boungiorno, MT:
Univ Hosp Mutua Terrassa, Fundacio Docencia & Recerca Mutua Terrassa, Barcelona, Spain
Univ Hosp Mutua Terrassa, Movement Disorders Unit, Dept Neurol, Barcelona, Spain
Buiza-Rueda, D:
Univ Seville, Hosp Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain
Cámara, A:
Hosp Clin Barcelona, Barcelona, Spain
Carrillo, F:
Univ Seville, Hosp Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain
Carrión-Claro, M:
Univ Seville, Hosp Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain
Cerdan, D:
Hosp Gen Segovia, Segovia, Spain
Clarimón, J:
Univ Autonoma Barcelona, Hosp Santa Cruz & San Pablo, Dept Neurol, Memory Unit,IIB Sant Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Compta, Y:
Hosp Clin Barcelona, Barcelona, Spain
de la Casa, B:
Hosp Gregorio Maranon, Madrid, Spain
Diez-Fairen, M:
Univ Hosp Mutua Terrassa, Fundacio Docencia & Recerca Mutua Terrassa, Barcelona, Spain
Univ Hosp Mutua Terrassa, Movement Disorders Unit, Dept Neurol, Barcelona, Spain
Dols-Icardo, O:
Univ Autonoma Barcelona, Hosp Santa Cruz & San Pablo, Dept Neurol, Memory Unit,IIB Sant Pau, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, CIBERNED, Madrid, Spain
Duarte, J:
Hosp Gen Segovia, Segovia, Spain
Duran, R:
Univ Granada, Ctr Invest Biomed, Granada, Spain
Escamilla-Sevilla, F:
Hosp Univ Virgen Las Nieves, Inst Invest Biosanit Granada, Granada, Spain
Feliz, C:
Inst Invest Sanit Fdn Jimenez Diaz, Dept Neurol, Madrid, Spain
Fernández, M:
Hosp Clin Barcelona, Barcelona, Spain
Fernández-Santiago, R:
Inst Invest Biomed August Pi & Sunyer, Lab Parkinson Dis & Other Neurodegenerat Movemen, Barcelona, Catalonia, Spain
Hosp Clin Barcelona, Neurol Serv, Barcelona, Catalonia, Spain
Networked Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain
Hosp Clin Barcelona, Barcelona, Spain
Garcia, C:
Hosp Univ Cent Asturias, Oviedo, Spain
García-Ruiz, P:
Inst Invest Sanitaria Fdn Jimenez Diaz, Madrid, Spain
Gómez-Garre, P:
Univ Seville, Hosp Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain
Heredia, MJG:
Hosp Univ Virgen Victoria, Malaga, Spain
Gonzalez-Aramburu, I:
Hosp Univ Marques Valdecilla IDIVAL, Santander, Spain
Pagola, AG:
Inst Invest Sanitaria Biodonostia, San Sebastian, Spain
Hoenicka J:
Inst Recerca Sanitaria Joan Deu, Barcelona, Spain
Univ Cantabria, Santander, Spain
Infante, J:
Ctr Invest Biomed Red Enfermedades Neurodegenerat, CIBERNED, Madrid, Spain
Hosp Univ Marques Valdecilla IDIVAL, Santander, Spain
Jesús, S:
Univ Seville, Hosp Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain
Jimenez-Escrig, A:
Hosp Univ Ramon & Cajal, Madrid, Spain
Kulisevsky, J:
Ctr Invest Biomed Red Enfermedades Neurodegenerat, CIBERNED, Madrid, Spain
Univ Autonoma Barcelona, Movement Disorders Unit, Hosp Santa Cruz & St Pau, Dept Neurol,IIB St Pau, Barcelona, Spain
Labrador-Espinosa, MA:
Univ Seville, Hosp Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain
Lopez-Sendon, JL:
Hosp Univ Ramon & Cajal, Madrid, Spain
Arregui, ALD:
Inst Invest Sanitaria Biodonostia, San Sebastian, Spain
Macias, D:
Univ Seville, Hosp Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain
Torres, IM:
Hosp Univ & Politecn La Fe, Dept Neurol, Inst Invest Sanitaria La Fe, Valencia, Spain
Marín, J:
Ctr Invest Biomed Red Enfermedades Neurodegenerat, CIBERNED, Madrid, Spain
Univ Autonoma Barcelona, Movement Disorders Unit, Hosp Santa Cruz & St Pau, Dept Neurol,IIB St Pau, Barcelona, Spain
Marti, MJ:
Hosp Clin Barcelona, Barcelona, Spain
Martínez-Castrillo, C:
Hosp Univ Ramon & Cajal, Inst Ramon & Cajal Invest Sanitaria, Madrid, Spain
Méndez-del-Barrio, C:
Univ Seville, Hosp Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain
González, MM:
Hosp Univ Cent Asturias, Oviedo, Spain
Mata, M:
Hosp Univ Infanta Sofia, Dept Neurol, Madrid, Spain
Mínguez, A:
Hosp Univ Virgen Las Nieves, Inst Invest Biosanit Granada, Granada, Spain
Mir, P:
Univ Seville, Hosp Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain
Rezola, EM:
Inst Invest Sanitaria Biodonostia, San Sebastian, Spain
Muñoz, E:
Hosp Clin Barcelona, Barcelona, Spain
Pagonabarraga, J:
Ctr Invest Biomed Red Enfermedades Neurodegenerat, CIBERNED, Madrid, Spain
Univ Autonoma Barcelona, Movement Disorders Unit, Hosp Santa Cruz & St Pau, Dept Neurol,IIB St Pau, Barcelona, Spain
Pascual-Sedano, B:
Hosp Santa Creu & Sant Pau, Unidad Trastornos Movimiento, Barcelona, Spain
Pastor, P:
Univ Hosp Mutua Terrassa, Fundacio Docencia & Recerca Mutua Terrassa, Barcelona, Spain
Univ Hosp Mutua Terrassa, Movement Disorders Unit, Dept Neurol, Barcelona, Spain
Errazquin, FP:
Hosp Univ Virgen Victoria, Malaga, Spain
Perinán-Tocino, T:
Univ Seville, Hosp Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain
Ruiz-Martínez, J:
Hosp Univ Donostia, Inst Invest Sanitaria Biodonostia, San Sebastian, Spain
Ruz, C:
Univ Granada, Ctr Invest Biomed, Granada, Spain
Rodriguez, AS:
Hosp Univ Marques Valdecilla IDIVAL, Santander, Spain
Sierra, M:
Hosp Univ Marques Valdecilla, Inst Invest Valdecilla IDIVAL, Santander, Spain
Suarez-Sanmartin, E:
Hosp Univ Cent Asturias, Oviedo, Spain
Tabernero, C:
Hosp Gen Segovia, Segovia, Spain
Tartari, JP:
Univ Hosp Mutua Terrassa, Fundacio Docencia & Recerca Mutua Terrassa, Barcelona, Spain
Univ Hosp Mutua Terrassa, Movement Disorders Unit, Dept Neurol, Barcelona, Spain
Tejera-Parrado, C:
Univ Seville, Hosp Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain
Tolosa, E:
Inst Invest Biomed August Pi & Sunyer, Lab Parkinson Dis & Other Neurodegenerat Movemen, Barcelona, Catalonia, Spain
Hosp Clin Barcelona, Neurol Serv, Barcelona, Catalonia, Spain
Networked Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain
Hosp Clin Barcelona, Barcelona, Spain
Valldeoriola, F:
Hosp Clin Barcelona, Barcelona, Spain
Vargas-González, L:
Univ Seville, Hosp Univ Virgen Rocio, CSIC, Inst Biomed Sevilla IBiS, Seville, Spain
Vela, L:
Hosp Univ Fdn Alcorcon, Dept Neurol, Madrid, Spain
Vives, F:
Univ Granada, Ctr Invest Biomed, Granada, Spain
Zimprich, A:
Med Univ Vienna, Dept Neurol, Vienna, Austria
Pihlstrom, L:
Oslo Univ Hosp, Dept Neurol, Oslo, Norway
Toft, M:
Oslo Univ Hosp, Dept Neurol, Oslo, Norway
Oslo Univ Hosp, Inst Clin Med, Oslo, Norway
Koks, S:
Univ Tartu, Dept Pathophysiol, Tartu, Estonia
Estonian Univ Life Sci, Dept Reprod Biol, Tartu, Estonia
Taba, P:
Univ Tartu, Dept Neurol & Neurosurg, Tartu, Estonia
Hassin-Baer, S:
Chaim Sheba Med Ctr, Movement Disorders Inst, Dept Neurol, IL-5262101 Ramat Gan, Israel
Chaim Sheba Med Ctr, Sagol Neurosci Ctr, Tel Hashomer, IL-5262101 Ramat Gan, Israel
Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel
Martí, MJ:
Inst Invest Biomed August Pi & Sunyer, Lab Parkinson Dis & Other Neurodegenerat Movemen, Barcelona, Catalonia, Spain
Hosp Clin Barcelona, Neurol Serv, Barcelona, Catalonia, Spain
Networked Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain
Ezquerra, M:
Inst Invest Biomed August Pi & Sunyer, Lab Parkinson Dis & Other Neurodegenerat Movemen, Barcelona, Catalonia, Spain
Hosp Clin Barcelona, Neurol Serv, Barcelona, Catalonia, Spain
Networked Ctr Biomed Res Neurodegenerat Dis, Madrid, Spain
Hosp Clin Barcelona, Barcelona, Spain
Malagelada, C:
Univ Barcelona, Dept Biomed, Unit Biochem, Casanova 143,North Wing 3rd Floor, E-08036 Barcelona, Catalonia, Spain
Univ Barcelona, Inst Neurosci, Barcelona, Catalonia, Spain
Green Accepted
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