Validity and prognostic value of a polygenic risk score for parkinson’s disease

Sebastian Koch, Björn Hergen Laabs, Meike Kasten, Eva Juliane Vollstedt, Jos Becktepe, Norbert Brüggemann, Andre Franke, Ulrike M. Krämer, Gregor Kuhlenbäumer, Wolfgang Lieb, Brit Mollenhauer, Miriam Neis, Claudia Trenkwalder, Eva Schäffer, Tatiana Usnich, Michael Wittig, Christine Klein, Inke R. König, Katja Lohmann, Michael KrawczakAmke Caliebe

Research output: Contribution to journalArticlepeer-review

Abstract

Idiopathic Parkinson’s disease (PD) is a complex multifactorial disorder caused by the interplay of both genetic and non-genetic risk factors. Polygenic risk scores (PRSs) are one way to aggregate the effects of a large number of genetic variants upon the risk for a disease like PD in a single quantity. However, reassessment of the performance of a given PRS in independent data sets is a precondition for establishing the PRS as a valid tool to this end. We studied a previously pro-posed PRS for PD in a separate genetic data set, comprising 1914 PD cases and 4464 controls, and were able to replicate its ability to differentiate between cases and controls. We also assessed theo-retically the prognostic value of the PD-PRS, i.e., its ability to predict the development of PD in later life for healthy individuals. As it turned out, the PD-PRS alone can be expected to perform poorly in this regard. Therefore, we conclude that the PD-PRS could serve as an important research tool, but that meaningful PRS-based prognosis of PD at an individual level is not feasible.

Original languageEnglish (US)
Article number1859
JournalGenes
Volume12
Issue number12
DOIs
StatePublished - Dec 2021
Externally publishedYes

Keywords

  • Genetic risk
  • Parkinson’s disease
  • Polygenic risk score
  • Prognostic value
  • Replication
  • Validation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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