Validity and Prognostic Value of a Polygenic Risk Score for Parkinson’s Disease

• Published in: Genes Vol. 12; no. 12; p. 1859
• Main Authors: Koch, Sebastian, Laabs, Björn-Hergen, Kasten, Meike, Vollstedt, Eva-Juliane, Becktepe, Jos, Brüggemann, Norbert, Franke, Andre, Krämer, Ulrike M., Kuhlenbäumer, Gregor, Lieb, Wolfgang, Mollenhauer, Brit, Neis, Miriam, Trenkwalder, Claudia, Schäffer, Eva, Usnich, Tatiana, Wittig, Michael, Klein, Christine, König, Inke R., Lohmann, Katja, Krawczak, Michael, Caliebe, Amke
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.11.2021; MDPI
• Subjects: Age; Aged; Alzheimer's disease; data collection; Datasets; Female; genes; Genetic diversity; Genetic Predisposition to Disease - genetics; genetic variation; Genome-Wide Association Study - methods; Genomes; Humans; Male; Middle Aged; Movement disorders; Multifactorial Inheritance - genetics; Neurodegenerative diseases; Parkinson disease; Parkinson Disease - genetics; Parkinson Disease - pathology; Parkinson's disease; Phenotype; Polymorphism, Single Nucleotide - genetics; prediction; Prognosis; Quality control; Regression analysis; Risk Factors; Software; Germany; replication; prognostic value; polygenic risk score; Parkinson’s disease; validation; genetic risk
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes12121859

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 proposed 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 theoretically 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.