The Genetic Architecture of Parkinson Disease in Spain: Characterizing Population-Specific Risk, Differential Haplotype Structures, and Providing Etiologic Insight


Por: Bandres-Ciga, S, Ahmed, S, Sabir, MS, Blauwendraat, C, Adarmes-Gomez, AD, Bernal-Bernal, I, Bonilla-Toribio, M, Buiza-Rueda, D, Carrillo, F, Carrion-Claro, M, Gomez-Garre, P, Jesus, S, Labrador-Espinosa, MA, Macias, D, Mendez-del-Barrio, C, Perinan-Tocino, T, Tejera-Parrado, C, Vargas-Gonzalez, L, Diez-Fairen, M, Alvarez, I, Tartari, JP, Buongiorno, M, Aguilar, M, Gorostidi, A, Bergareche, JA, Mondragon, E, Vinagre-Aragon, A, Croitoru, I, Ruiz-Martinez, J, Dols-Icardo, O, Kulisevsky, J, Marin-Lahoz, J, Pagonabarraga, J, Pascual-Sedano, B, Ezquerra, M, Camara, A, Compta, Y, Fernandez, M, Fernandez-Santiago, R, Munoz, E, Tolosa, E, Valldeoriola, F, Gonzalez-Aramburu, I, Rodriguez, AS, Sierra, M, Menendez-Gonzalez, M, Blazquez, M, Garcia, C, Martin, ESS, Garcia-Ruiz, P, Martinez-Castrillo, JC, Vela-Desojo, L, Ruz, C, Barrero, FJ, Escamilla-Sevilla, F, Minguez-Castellanos, A, Cerdan, D, Tabernero, C, Heredia, MJG, Errazquin, FP, Romero-Acebal, M, Feliz, C, Lopez-Sendon, JL, Mata, M, Torres, IM, Kim, JJ, Dalgard, CL, Brooks, J, Saez-Atienzar, S, Gibbs, JR, Jorda, R, Botia, JA, Bonet-Ponce, L, Morrison, KE, Clarke, C, Tan, M, Morris, H, Edsall, C, Hernandez, D, Simon-Sanchez, J, Nalls, MA, Scholz, SW, Jimenez-Escrig, A, Duarte, J, Vives, F, Duran, R, Hoenicka, J, Alvarez, V, Infante, J, Marti, MJ, Clarimon, J, de Munain, AL, Pastor, P, Mir, P, Singleton, A

Publicada: 1 dic 2019 Ahead of Print: 1 oct 2019
Resumen:
Background The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases. Objectives To perform the largest PD genome-wide association study restricted to a single country. Methods We performed a GWAS for both risk of PD and age at onset in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression, and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations, and burden analyses. Results We identified a novel population-specific genome-wide association study signal at PARK2 associated with age at onset, which was likely dependent on the c.155delA mutation. We replicated four genome-wide independent signals associated with PD risk, including SNCA, LRRK2, KANSL1/MAPT, and HLA-DQB1. A significant trend for smaller risk haplotypes at known loci was found compared to similar studies of non-Spanish origin. Seventeen PD-related genes showed functional consequence by two-sample Mendelian randomization in expression and methylation data sets. Long runs of homozygosity at 28 known genes/loci were found to be enriched in cases versus controls. Conclusions Our data demonstrate the utility of the Spanish risk haplotype substructure for future fine-mapping efforts, showing how leveraging unique and diverse population histories can benefit genetic studies of complex diseases. The present study points to PARK2 as a major hallmark of PD etiology in Spain. (c) 2019 International Parkinson and Movement Disorder Society

Filiaciones:
Bandres-Ciga, S:
 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

 Inst Invest Biosanitaria Granada Ibs GRANADA, Granada, Spain

Ahmed, S:
 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

 NINCDS, Neurodegenerat Dis Res Unit, NIH, Bethesda, MD 20892 USA

Sabir, MS:
 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

 NINCDS, Neurodegenerat Dis Res Unit, NIH, Bethesda, MD 20892 USA

Blauwendraat, C:
 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

Adarmes-Gomez, AD:
 Univ Seville, Hosp Univ Virgen del Rocio, Serv Neurol & Neurofisiol Clin,CSIC, Unidad Trastornos Movimiento,Inst Biomed Sevilla, Seville, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Bernal-Bernal, I:
 Univ Seville, Hosp Univ Virgen del Rocio, Serv Neurol & Neurofisiol Clin,CSIC, Unidad Trastornos Movimiento,Inst Biomed Sevilla, Seville, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Bonilla-Toribio, M:
 Univ Seville, Hosp Univ Virgen del Rocio, Serv Neurol & Neurofisiol Clin,CSIC, Unidad Trastornos Movimiento,Inst Biomed Sevilla, Seville, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Buiza-Rueda, D:
 Univ Seville, Hosp Univ Virgen del Rocio, Serv Neurol & Neurofisiol Clin,CSIC, Unidad Trastornos Movimiento,Inst Biomed Sevilla, Seville, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Carrillo, F:
 Univ Seville, Hosp Univ Virgen del Rocio, Serv Neurol & Neurofisiol Clin,CSIC, Unidad Trastornos Movimiento,Inst Biomed Sevilla, Seville, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Carrion-Claro, M:
 Univ Seville, Hosp Univ Virgen del Rocio, Serv Neurol & Neurofisiol Clin,CSIC, Unidad Trastornos Movimiento,Inst Biomed Sevilla, Seville, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Gomez-Garre, P:
 Univ Seville, Hosp Univ Virgen del Rocio, Serv Neurol & Neurofisiol Clin,CSIC, Unidad Trastornos Movimiento,Inst Biomed Sevilla, Seville, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Jesus, S:
 Univ Seville, Hosp Univ Virgen del Rocio, Serv Neurol & Neurofisiol Clin,CSIC, Unidad Trastornos Movimiento,Inst Biomed Sevilla, Seville, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Labrador-Espinosa, MA:
 Univ Seville, Hosp Univ Virgen del Rocio, Serv Neurol & Neurofisiol Clin,CSIC, Unidad Trastornos Movimiento,Inst Biomed Sevilla, Seville, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Macias, D:
 Univ Seville, Hosp Univ Virgen del Rocio, Serv Neurol & Neurofisiol Clin,CSIC, Unidad Trastornos Movimiento,Inst Biomed Sevilla, Seville, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Mendez-del-Barrio, C:
 Univ Seville, Hosp Univ Virgen del Rocio, Serv Neurol & Neurofisiol Clin,CSIC, Unidad Trastornos Movimiento,Inst Biomed Sevilla, Seville, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Perinan-Tocino, T:
 Univ Seville, Hosp Univ Virgen del Rocio, Serv Neurol & Neurofisiol Clin,CSIC, Unidad Trastornos Movimiento,Inst Biomed Sevilla, Seville, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Tejera-Parrado, C:
 Univ Seville, Hosp Univ Virgen del Rocio, Serv Neurol & Neurofisiol Clin,CSIC, Unidad Trastornos Movimiento,Inst Biomed Sevilla, Seville, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Vargas-Gonzalez, L:
 Univ Seville, Hosp Univ Virgen del Rocio, Serv Neurol & Neurofisiol Clin,CSIC, Unidad Trastornos Movimiento,Inst Biomed Sevilla, Seville, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, 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

Alvarez, I:
 Univ Hosp Mutua Terrassa, Fundacio Docencia & Recerca Mutua Terrassa, Barcelona, Spain

 Univ Hosp Mutua Terrassa, Movement Disorders Unit, Dept Neurol, Barcelona, 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

Buongiorno, M:
 Univ Hosp Mutua Terrassa, Fundacio Docencia & Recerca Mutua Terrassa, Barcelona, Spain

 Univ Hosp Mutua Terrassa, Movement Disorders Unit, Dept Neurol, Barcelona, Spain

Aguilar, M:
 Univ Hosp Mutua Terrassa, Fundacio Docencia & Recerca Mutua Terrassa, Barcelona, Spain

 Univ Hosp Mutua Terrassa, Movement Disorders Unit, Dept Neurol, Barcelona, Spain

Gorostidi, A:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 Biodonostia Hlth Res Inst, Neurodegenerat Disorders Area, San Sebastian, Spain

 Inst Invest Biodonostia, Plataforma Genom, San Sebastian, Spain

Bergareche, JA:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 Biodonostia Hlth Res Inst, Neurodegenerat Disorders Area, San Sebastian, Spain

 Hosp Univ Donostia, Unidad Trastornos Movimiento, Dept Neurol, San Sebastian, Spain

Mondragon, E:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 Biodonostia Hlth Res Inst, Neurodegenerat Disorders Area, San Sebastian, Spain

 Hosp Univ Donostia, Unidad Trastornos Movimiento, Dept Neurol, San Sebastian, Spain

Vinagre-Aragon, A:
 Hosp Univ Donostia, Unidad Trastornos Movimiento, Dept Neurol, San Sebastian, Spain

Croitoru, I:
 Biodonostia Hlth Res Inst, Neurodegenerat Disorders Area, San Sebastian, Spain

Ruiz-Martinez, J:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 Biodonostia Hlth Res Inst, Neurodegenerat Disorders Area, San Sebastian, Spain

 Hosp Univ Donostia, Unidad Trastornos Movimiento, Dept Neurol, San Sebastian, Spain

Dols-Icardo, O:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 IIB St Pau, Genet Neurodegenerat Disorders Unit, Barcelona, Catalonia, Spain

 Univ Autonoma Barcelona, Barcelona, Catalonia, Spain

Kulisevsky, J:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 Univ Autonoma Barcelona, Movement Disorders Unit, Dept Neurol, St Pau Hosp, Barcelona, Catalonia, Spain

Marin-Lahoz, J:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 Univ Autonoma Barcelona, Movement Disorders Unit, Dept Neurol, St Pau Hosp, Barcelona, Catalonia, Spain

Pagonabarraga, J:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 Univ Autonoma Barcelona, Movement Disorders Unit, Dept Neurol, St Pau Hosp, Barcelona, Catalonia, Spain

Pascual-Sedano, B:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 Univ Autonoma Barcelona, Movement Disorders Unit, Dept Neurol, St Pau Hosp, Barcelona, Catalonia, Spain

Ezquerra, M:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 IDIBAPS Inst Invest Biomed, Lab Parkinson Dis & Other Neurodegenerat Movement, Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Unitat Parkinson & Trastorns Moviment, Serv Neurol,Hosp Clin Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Inst Neurociencies, Catalonia, Spain

Camara, A:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 IDIBAPS Inst Invest Biomed, Lab Parkinson Dis & Other Neurodegenerat Movement, Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Unitat Parkinson & Trastorns Moviment, Serv Neurol,Hosp Clin Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Inst Neurociencies, Catalonia, Spain

Compta, Y:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 IDIBAPS Inst Invest Biomed, Lab Parkinson Dis & Other Neurodegenerat Movement, Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Unitat Parkinson & Trastorns Moviment, Serv Neurol,Hosp Clin Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Inst Neurociencies, Catalonia, Spain

Fernandez, M:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 IDIBAPS Inst Invest Biomed, Lab Parkinson Dis & Other Neurodegenerat Movement, Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Unitat Parkinson & Trastorns Moviment, Serv Neurol,Hosp Clin Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Inst Neurociencies, Catalonia, Spain

Fernandez-Santiago, R:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 IDIBAPS Inst Invest Biomed, Lab Parkinson Dis & Other Neurodegenerat Movement, Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Unitat Parkinson & Trastorns Moviment, Serv Neurol,Hosp Clin Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Inst Neurociencies, Catalonia, Spain

Munoz, E:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 IDIBAPS Inst Invest Biomed, Lab Parkinson Dis & Other Neurodegenerat Movement, Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Unitat Parkinson & Trastorns Moviment, Serv Neurol,Hosp Clin Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Inst Neurociencies, Catalonia, Spain

Tolosa, E:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 IDIBAPS Inst Invest Biomed, Lab Parkinson Dis & Other Neurodegenerat Movement, Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Unitat Parkinson & Trastorns Moviment, Serv Neurol,Hosp Clin Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Inst Neurociencies, Catalonia, Spain

Valldeoriola, F:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 IDIBAPS Inst Invest Biomed, Lab Parkinson Dis & Other Neurodegenerat Movement, Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Unitat Parkinson & Trastorns Moviment, Serv Neurol,Hosp Clin Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Inst Neurociencies, Catalonia, Spain

Gonzalez-Aramburu, I:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 Hosp Univ Marques Valdecilla IDIVAL, Serv Neurol, Santander, Spain

 Univ Cantabria, Santander, Spain

Rodriguez, AS:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 Hosp Univ Marques Valdecilla IDIVAL, Serv Neurol, Santander, Spain

 Univ Cantabria, Santander, Spain

Sierra, M:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 Hosp Univ Marques Valdecilla IDIVAL, Serv Neurol, Santander, Spain

 Univ Cantabria, Santander, Spain

Menendez-Gonzalez, M:
 Hosp Univ Cent Asturias, Serv Neurol, Asturias, Spain

 Inst Invest Sanitaria Principado Asturias ISPA, Asturias, Spain

Blazquez, M:
 Hosp Univ Cent Asturias, Serv Neurol, Asturias, Spain

 Inst Invest Sanitaria Principado Asturias ISPA, Asturias, Spain

Garcia, C:
 Hosp Univ Cent Asturias, Serv Neurol, Asturias, Spain

 Inst Invest Sanitaria Principado Asturias ISPA, Asturias, Spain

Martin, ESS:
 Hosp Univ Cent Asturias, Serv Neurol, Asturias, Spain

 Inst Invest Sanitaria Principado Asturias ISPA, Asturias, Spain

Garcia-Ruiz, P:
 Inst Invest Sanitaria Fdn Jimenez Diaz, Dept Neurol, Madrid, Spain

Martinez-Castrillo, JC:
 Hosp Univ Ramon y Cajal, Dept Neurol, Inst Ramon y Cajal Invest Sanitaria, Madrid, Spain

Vela-Desojo, L:
 Hosp Univ Fdn Alcorcon, Serv Neurol, Madrid, Spain

Ruz, C:
 Inst Invest Biosanitaria Granada Ibs GRANADA, Granada, Spain

 Univ Granada, Ctr Invest Biomed, Fac Med, Granada, Spain

 Univ Granada, Dept Fisiol, Fac Med, Granada, Spain

Barrero, FJ:
 Inst Invest Biosanitaria Granada Ibs GRANADA, Granada, Spain

 Univ Granada, Hosp Univ San Cecilio, Serv Neurol, Granada, Spain

Escamilla-Sevilla, F:
 Inst Invest Biosanitaria Granada Ibs GRANADA, Granada, Spain

 Hosp Univ Virgen de las Nieves, Serv Neurol, Granada, Spain

Minguez-Castellanos, A:
 Inst Invest Biosanitaria Granada Ibs GRANADA, Granada, Spain

 Hosp Univ Virgen de las Nieves, Serv Neurol, Granada, Spain

Cerdan, D:
 Hosp Gen Segovia, Serv Neurol, Segovia, Spain

Tabernero, C:
 Hosp Gen Segovia, Serv Neurol, Segovia, Spain

Heredia, MJG:
 Hosp Univ Virgen de la Victoria, Serv Neurol, Malaga, Spain

Errazquin, FP:
 Hosp Univ Virgen de la Victoria, Serv Neurol, Malaga, Spain

Romero-Acebal, M:
 Hosp Univ Virgen de la Victoria, Serv Neurol, Malaga, Spain

Feliz, C:
 Inst Invest Sanitaria Fdn Jimenez Diaz, Dept Neurol, Madrid, Spain

Lopez-Sendon, JL:
 Hosp Univ Ramon y Cajal, Dept Neurol, Inst Ramon y Cajal Invest Sanitaria, Madrid, Spain

Mata, M:
 Hosp Univ Infanta Sofia, Dept Neurol, Madrid, Spain

Torres, IM:
 Hosp Univ & Politecn La Fe, Dept Neurol, Inst Invest Sanitaria La Fe, Valencia, Spain

Kim, JJ:
 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

Dalgard, CL:
 Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA

 Uniformed Serv Univ Hlth Sci, Amer Genome Ctr, Collaborat Hlth Initiat Res Program, Bethesda, MD 20814 USA

Brooks, J:
 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

Saez-Atienzar, S:
 NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

Gibbs, JR:
 NIA, Computat Biol Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

Jorda, R:
 Univ Murcia, Dept Ingn Informac & Comunicac, Murcia, Spain

Botia, JA:
 Univ Murcia, Dept Ingn Informac & Comunicac, Murcia, Spain

 UCL, Inst Neurol, Dept Mol Neurosci, London, England

Bonet-Ponce, L:
 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

Morrison, KE:
 Univ Southampton, Dept Neurol, Fac Med, Southampton, Hants, England

Clarke, C:
 Univ Birmingham, Birmingham, W Midlands, England

 Sandwell & West Birmingham Hosp NHS Trust, Birmingham, W Midlands, England

Tan, M:
 UCL, Dept Clin Neurosci, London, England

Morris, H:
 UCL, Dept Clin Neurosci, London, England

Edsall, C:
 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

Hernandez, D:
 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

Simon-Sanchez, J:
 Univ Tubingen, Dept Neurodegenerat Dis, Hertie Inst Clin Brain Res, Tubingen, Germany

 German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany

Nalls, MA:
 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

 Data Tecn Int, Glen Echo, MD USA

Scholz, SW:
 NINCDS, Neurodegenerat Dis Res Unit, NIH, Bethesda, MD 20892 USA

 Johns Hopkins Med Ctr, Dept Neurol, Baltimore, MD USA

Jimenez-Escrig, A:
 Hosp Univ Ramon y Cajal, Dept Neurol, Inst Ramon y Cajal Invest Sanitaria, Madrid, Spain

Duarte, J:
 Hosp Gen Segovia, Serv Neurol, Segovia, Spain

Vives, F:
 Inst Invest Biosanitaria Granada Ibs GRANADA, Granada, Spain

 Univ Granada, Ctr Invest Biomed, Fac Med, Granada, Spain

 Univ Granada, Dept Fisiol, Fac Med, Granada, Spain

Duran, R:
 Inst Invest Biosanitaria Granada Ibs GRANADA, Granada, Spain

 Univ Granada, Ctr Invest Biomed, Fac Med, Granada, Spain

 Univ Granada, Dept Fisiol, Fac Med, Granada, Spain

Hoenicka, J:
 Inst Recerca St Joan Deu, Lab Neurogenet & Med Mol, Barcelona, Spain

 Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain

Alvarez, V:
 Inst Invest Sanitaria Principado Asturias ISPA, Asturias, Spain

 Hosp Univ Cent Asturias, Genet Lab, Asturias, Spain

Infante, J:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 Hosp Univ Marques Valdecilla IDIVAL, Serv Neurol, Santander, Spain

 Univ Cantabria, Santander, Spain

Marti, MJ:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 IDIBAPS Inst Invest Biomed, Lab Parkinson Dis & Other Neurodegenerat Movement, Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Unitat Parkinson & Trastorns Moviment, Serv Neurol,Hosp Clin Barcelona, Catalonia, Spain

 Univ Barcelona, Maria de Maetzu Ctr, Inst Neurociencies, Catalonia, Spain

Clarimon, J:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 IIB St Pau, Genet Neurodegenerat Disorders Unit, Barcelona, Catalonia, Spain

 Univ Autonoma Barcelona, Barcelona, Catalonia, Spain

de Munain, AL:
 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

 Biodonostia Hlth Res Inst, Neurodegenerat Disorders Area, San Sebastian, Spain

 Univ Basque Country, Hosp Univ Donostia, Serv Neurol, Dept Neurociencias, San Sebastian, 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

Mir, P:
 Univ Seville, Hosp Univ Virgen del Rocio, Serv Neurol & Neurofisiol Clin,CSIC, Unidad Trastornos Movimiento,Inst Biomed Sevilla, Seville, Spain

 Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

Singleton, A:
 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
ISSN: 08853185
Editorial
WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Estados Unidos America
Tipo de documento: Article
Volumen: 34 Número: 12
Páginas: 1851-1863
WOS Id: 000492990700001
ID de PubMed: 31660654
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