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Finnish Parkinson's disease study integrating protein-protein interaction network data with exome sequencing analysis.
Siitonen, Ari; Kytövuori, Laura; Nalls, Mike A; Gibbs, Raphael; Hernandez, Dena G; Ylikotila, Pauli; Peltonen, Markku; Singleton, Andrew B; Majamaa, Kari.
Afiliação
  • Siitonen A; Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland. Ari.Siitonen@iki.fi.
  • Kytövuori L; Department of Neurology and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland. Ari.Siitonen@iki.fi.
  • Nalls MA; Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland.
  • Gibbs R; Department of Neurology and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
  • Hernandez DG; Laboratory for Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Ylikotila P; Data Tecnica International, Glen Echo, MD, 20812, USA.
  • Peltonen M; Laboratory for Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Singleton AB; Laboratory for Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • Majamaa K; Institute of Clinical Medicine, Department of Neurology, University of Turku, Turku, Finland.
Sci Rep ; 9(1): 18865, 2019 12 11.
Article em En | MEDLINE | ID: mdl-31827228
Variants associated with Parkinson's disease (PD) have generally a small effect size and, therefore, large sample sizes or targeted analyses are required to detect significant associations in a whole exome sequencing (WES) study. Here, we used protein-protein interaction (PPI) information on 36 genes with established or suggested associations with PD to target the analysis of the WES data. We performed an association analysis on WES data from 439 Finnish PD subjects and 855 controls, and included a Finnish population cohort as the replication dataset with 60 PD subjects and 8214 controls. Single variant association (SVA) test in the discovery dataset yielded 11 candidate variants in seven genes, but the associations were not significant in the replication cohort after correction for multiple testing. Polygenic risk score using variants rs2230288 and rs2291312, however, was associated to PD with odds ratio of 2.7 (95% confidence interval 1.4-5.2; p < 2.56e-03). Furthermore, an analysis of the PPI network revealed enriched clusters of biological processes among established and candidate genes, and these functional networks were visualized in the study. We identified novel candidate variants for PD using a gene prioritization based on PPI information, and described why these variants may be involved in the pathogenesis of PD.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Mapas de Interação de Proteínas Tipo de estudo: Prognostic_studies Limite: Female / Humans / Male País/Região como assunto: Europa Idioma: En Revista: Sci Rep Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Finlândia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Mapas de Interação de Proteínas Tipo de estudo: Prognostic_studies Limite: Female / Humans / Male País/Região como assunto: Europa Idioma: En Revista: Sci Rep Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Finlândia