A1 Refereed original research article in a scientific journal
Finnish Parkinson's disease study integrating protein-protein interaction network data with exome sequencing analysis
Authors: Ari Siitonen, Laura Kytövuori, Mike A. Nalls, Raphael Gibbs, Dena G. Hernandez, Pauli Ylikotila, Markku Peltonen, Andrew B. Singleton, Kari Majamaa
Publisher: NATURE PUBLISHING GROUP
Publication year: 2019
Journal: Scientific Reports
Journal name in source: SCIENTIFIC REPORTS
Journal acronym: SCI REP-UK
Article number: ARTN 18865
Volume: 9
Number of pages: 8
ISSN: 2045-2322
eISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-019-55479-y(external)
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/44980479(external)
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.
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