RT Journal Article
T1 The Genetic Architecture of Parkinson Disease in Spain: Characterizing Population-Specific Risk, Differential Haplotype Structures, and Providing Etiologic Insight.
A1 Bandres-Ciga, Sara
A1 Ahmed, Sarah
A1 Sabir, Marya S
A1 Blauwendraat, Cornelis
A1 Adarmes-Gómez, Astrid D
A1 Bernal-Bernal, Inmaculada
A1 Bonilla-Toribio, Marta
A1 Buiza-Rueda, Dolores
A1 Carrillo, Fátima
A1 Carrión-Claro, Mario
A1 Gómez-Garre, Pilar
A1 Jesús, Silvia
A1 Labrador-Espinosa, Miguel A
A1 Macias, Daniel
A1 Méndez-Del-Barrio, Carlota
A1 Periñán-Tocino, Teresa
A1 Tejera-Parrado, Cristina
A1 Vargas-González, Laura
A1 Diez-Fairen, Monica
A1 Alvarez, Ignacio
A1 Tartari, Juan Pablo
A1 Buongiorno, Mariateresa
A1 Aguilar, Miquel
A1 Gorostidi, Ana
A1 Bergareche, Jesús Alberto
A1 Mondragon, Elisabet
A1 Vinagre-Aragon, Ana
A1 Croitoru, Ioana
A1 Ruiz-Martínez, Javier
A1 Dols-Icardo, Oriol
A1 Kulisevsky, Jaime
A1 Marín-Lahoz, Juan
A1 Pagonabarraga, Javier
A1 Pascual-Sedano, Berta
A1 Ezquerra, Mario
A1 Cámara, Ana
A1 Compta, Yaroslau
A1 Fernández, Manel
A1 Fernández-Santiago, Rubén
A1 Muñoz, Esteban
A1 Tolosa, Eduard
A1 Valldeoriola, Francesc
A1 Gonzalez-Aramburu, Isabel
A1 Sanchez Rodriguez, Antonio
A1 Sierra, María
A1 Menéndez-González, Manuel
A1 Blazquez, Marta
A1 Garcia, Ciara
A1 Suarez-San Martin, Esther
A1 García-Ruiz, Pedro
A1 Martínez-Castrillo, Juan Carlos
A1 Vela-Desojo, Lydia
A1 Ruz, Clara
A1 Barrero, Francisco Javier
A1 Escamilla-Sevilla, Francisco
A1 Mínguez-Castellanos, Adolfo
A1 Cerdan, Debora
A1 Tabernero, Cesar
A1 Gomez Heredia, Maria Jose
A1 Perez Errazquin, Francisco
A1 Romero-Acebal, Manolo
A1 Feliz, Cici
A1 Lopez-Sendon, Jose Luis
A1 Mata, Marina
A1 Martínez Torres, Irene
A1 Kim, Jonggeol Jeffrey
A1 Dalgard, Clifton L
A1 American Genome Center, 
A1 Brooks, Janet
A1 Saez-Atienzar, Sara
A1 Gibbs, J Raphael
A1 Jorda, Rafael
A1 Botia, Juan A
A1 Bonet-Ponce, Luis
A1 Morrison, Karen E
A1 Clarke, Carl
A1 Tan, Manuela
A1 Morris, Huw
A1 Edsall, Connor
A1 Hernandez, Dena
A1 Simon-Sanchez, Javier
A1 Nalls, Mike A
A1 Scholz, Sonja W
A1 Jimenez-Escrig, Adriano
A1 Duarte, Jacinto
A1 Vives, Francisco
A1 Duran, Raquel
A1 Hoenicka, Janet
A1 Alvarez, Victoria
A1 Infante, Jon
A1 Marti, Maria José
A1 Clarimón, Jordi
A1 López de Munain, Adolfo
A1 Pastor, Pau
A1 Mir, Pablo
A1 Singleton, Andrew
A1 International Parkinson Disease Genomics Consortium, 
K1 Parkinson's disease
K1 Spanish population
K1 age at onset
K1 polygenic risk score
K1 risk haplotype
AB 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. To perform the largest PD genome-wide association study restricted to a single country. 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. 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. 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. © 2019 International Parkinson and Movement Disorder Society.
YR 2019
FD 2019-10-29
LK http://hdl.handle.net/10668/15500
UL http://hdl.handle.net/10668/15500
LA en
DS RISalud
RD Apr 11, 2025