Universidad Peruana Cayetano Heredia

Polygenic risk prediction and SNCA haplotype analysis in a Latino Parkinson's disease cohort

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dc.contributor.author Loesch, Douglas P.
dc.contributor.author Horimoto, Andrea R. V. R.
dc.contributor.author Sarihan, Elif Irem
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 Thornton, Timothy A.
dc.contributor.author Mata, Ignacio F.
dc.contributor.author O'Connor, Timothy D.
dc.contributor.author International Parkinson Disease Genomics Consortium (IPDGC)
dc.contributor.author Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE-PD)
dc.date.accessioned 2022-09-09T18:52:23Z
dc.date.available 2022-09-09T18:52:23Z
dc.date.issued 2022
dc.identifier.uri https://hdl.handle.net/20.500.12866/12163
dc.description.abstract Background: Large-scale Parkinson's disease (PD) genome-wide association studies (GWAS) have, until recently, only been conducted on subjects with European-ancestry. Consequently, polygenic risk scores (PRS) constructed using PD GWAS data are likely to be less predictive when applied to non-European cohorts. Methods: Using GWAS data from the largest study to date, we constructed a PD PRS for a Latino PD cohort (1497 subjects from LARGE-PD) and tested it for association with PD status and age at onset. We validated the PRS performance by testing it in an independent Latino cohort (448 subjects) and by repeating the analysis in LARGE-PD with the addition of 440 external Peruvian controls. We also tested SNCA haplotypes for association with PD risk in LARGE-PD and a European-ancestry PD cohort. Results: The GWAS-significant PD PRS had an area under the receiver-operator curve (AUC) of 0.668 (95% CI: 0.640–0.695) in LARGE-PD. The inclusion of external Peruvian controls mitigated this result, dropping the AUC 0.632 (95% CI: 0.607–0.657). At the SNCA locus, haplotypes differ by ancestry. Ancestry-specific SNCA haplotypes were associated with PD status in both LARGE-PD and the European-ancestry cohort (p-value < 0.05). These haplotypes both include the rs356182 G-allele, but only share 14% of their variants overall. Conclusion: The PD PRS has potential for PD risk prediction in Latinos, but variability caused by admixture patterns and bias in a European-ancestry PD PRS data limits its utility. The inclusion of diverse subjects can help elucidate PD risk loci and improve risk prediction in non-European cohorts. en_US
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartofseries Parkinsonism and Related Disorders
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Polygenic risk prediction en_US
dc.subject SNCA haplotype analysis en_US
dc.subject Parkinson's disease en_US
dc.subject Cohort en_US
dc.title Polygenic risk prediction and SNCA haplotype analysis in a Latino Parkinson's disease cohort en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1016/j.parkreldis.2022.06.010
dc.relation.issn 1873-5126


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