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Characterizing the Genetic Architecture of Parkinson's Disease in Latinos

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dc.contributor.author Loesch, Douglas P.
dc.contributor.author Horimoto, Andrea R. V. R.
dc.contributor.author Heilbron, Karl
dc.contributor.author Sarihan, Elif I.
dc.contributor.author Inca-Martinez, Miguel
dc.contributor.author Mason, Emily
dc.contributor.author Cornejo-Olivas, Mario
dc.contributor.author Torres, Luis
dc.contributor.author Mazzetti, Pilar
dc.contributor.author Cosentino, Carlos
dc.contributor.author Sarapura-Castro, Elison
dc.contributor.author Rivera-Valdivia, Andrea
dc.contributor.author Medina, Angel C.
dc.contributor.author Dieguez, Elena
dc.contributor.author Raggio, Victor
dc.contributor.author Lescano, Andrés
dc.contributor.author Tumas, Vitor
dc.contributor.author Borges, Vanderci
dc.contributor.author Ferraz, Henrique B.
dc.contributor.author Rieder, Carlos R.
dc.contributor.author Schumacher-Schuh, Artur
dc.contributor.author Santos-Lobato, Bruno L.
dc.contributor.author Velez-Pardo, Carlos
dc.contributor.author Jimenez-Del-Rio, Marlene
dc.contributor.author Lopera, Francisco
dc.contributor.author Moreno, Sonia
dc.contributor.author Chana-Cuevas, Pedro
dc.contributor.author Fernandez, William
dc.contributor.author Arboleda, Gonzalo
dc.contributor.author Arboleda, Humberto
dc.contributor.author Arboleda-Bustos, Carlos E.
dc.contributor.author Yearout, Dora
dc.contributor.author Zabetian, Cyrus P.
dc.contributor.author Cannon, Paul
dc.contributor.author Thornton, Timothy A.
dc.contributor.author O'Connor, Timothy D.
dc.contributor.author Mata, Ignacio F.
dc.contributor.author Latin Amer Res Consortium Genetics
dc.date.accessioned 2021-10-04T23:00:56Z
dc.date.available 2021-10-04T23:00:56Z
dc.date.issued 2021
dc.identifier.uri https://hdl.handle.net/20.500.12866/9794
dc.description.abstract Objective This work was undertaken in order to identify Parkinson's disease (PD) risk variants in a Latino cohort, to describe the overlap in the genetic architecture of PD in Latinos compared to European-ancestry subjects, and to increase the diversity in PD genome-wide association (GWAS) data. Methods We genotyped and imputed 1,497 PD cases and controls recruited from nine clinical sites across South America. We performed a GWAS using logistic mixed models; variants with a p-value <1 x 10(-5) were tested in a replication cohort of 1,234 self-reported Latino PD cases and 439,522 Latino controls from 23andMe, Inc. We also performed an admixture mapping analysis where local ancestry blocks were tested for association with PD status. Results One locus, SNCA, achieved genome-wide significance (p-value <5 x 10(-8)); rs356182 achieved genome-wide significance in both the discovery and the replication cohorts (discovery, G allele: 1.58 OR, 95% CI 1.35-1.86, p-value 2.48 x 10(-8); 23andMe, G allele: 1.26 OR, 95% CI 1.16-1.37, p-value 4.55 x 10(-8)). In our admixture mapping analysis, a locus on chromosome 14, containing the gene STXBP6, achieved significance in a joint test of ancestries and in the Native American single-ancestry test (p-value <5 x 10(-5)). A second locus on chromosome 6, containing the gene RPS6KA2, achieved significance in the African single-ancestry test (p-value <5 x 10(-5)). Interpretation This study demonstrated the importance of the SNCA locus for the etiology of PD in Latinos. By leveraging the demographic history of our cohort via admixture mapping, we identified two potential PD risk loci that merit further study en_US
dc.language.iso eng
dc.publisher Wiley
dc.relation.ispartofseries Annals of Neurology
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Genetic Architecture en_US
dc.subject Parkinson's Disease en_US
dc.subject Latinos en_US
dc.title Characterizing the Genetic Architecture of Parkinson's Disease in Latinos en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1002/ana.26153
dc.relation.issn 1531-8249


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