Characterizing the Genetic Architecture of Parkinson's Disease in Latinos

Lescano, Andrés; Cornejo-Olivas, Mario; Chana-Cuevas, Pedro; Horimoto, Andrea R. V. R.; Fernandez, William; Ferraz, Henrique B.; Velez-Pardo, Carlos; Cosentino, Carlos; Sarapura-Castro, Elison; O'Connor, Timothy D.; Latin Amer Res Consortium Genetics; Thornton, Timothy A.; Arboleda, Humberto; Rivera-Valdivia, Andrea; Yearout, Dora; Torres, Luis; Rieder, Carlos R.; Mason, Emily; Arboleda, Gonzalo; Sarihan, Elif I.; Schumacher-Schuh, Artur; Mata, Ignacio F.; Santos-Lobato, Bruno L.; Loesch, Douglas P.; Lopera, Francisco; Borges, Vanderci; Zabetian, Cyrus P.; Inca-Martinez, Miguel; Raggio, Victor; Moreno, Sonia; Heilbron, Karl; Mazzetti, Pilar; Arboleda-Bustos, Carlos E.; Jimenez-Del-Rio, Marlene; Cannon, Paul; Tumas, Vitor; Medina, Angel C.; Dieguez, Elena

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.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.subject.ocde	https://purl.org/pe-repo/ocde/ford#3.02.25
dc.relation.issn	1531-8249