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 Krawczak; Amke Caliebe

doi:10.3390/genes12121859

Genes (Nov 2021)

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 Krawczak,
Amke Caliebe

Affiliations

Sebastian Koch: Institute of Medical Informatics and Statistics, Kiel University, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
Björn-Hergen Laabs: Institute of Medical Biometry and Statistics, University of Luebeck, University Medical Center Schleswig-Holstein, Campus Luebeck, 23562 Luebeck, Germany
Meike Kasten: Department of Psychiatry, University of Luebeck, 23538 Luebeck, Germany
Eva-Juliane Vollstedt: Institute of Neurogenetics, University of Luebeck, University Medical Center Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, Germany
Jos Becktepe: Department of Neurology, Kiel University, 24105 Kiel, Germany
Norbert Brüggemann: Institute of Neurogenetics, University of Luebeck, University Medical Center Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, Germany
Andre Franke: Institute of Clinical Molecular Biology, Kiel University, 24105 Kiel, Germany
Ulrike M. Krämer: Department of Neurology, University of Luebeck, 23562 Luebeck, Germany
Gregor Kuhlenbäumer: Department of Neurology, Kiel University, 24105 Kiel, Germany
Wolfgang Lieb: Institute of Epidemiology and PopGen Biobank, Kiel University, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
Brit Mollenhauer: Department of Neurology, University Medical Center Goettingen, 37075 Goettingen, Germany
Miriam Neis: Department of Neurology, University of Luebeck, 23562 Luebeck, Germany
Claudia Trenkwalder: Paracelsus-Elena-Klinik, 34128 Kassel, Germany
Eva Schäffer: Department of Neurology, Kiel University, 24105 Kiel, Germany
Tatiana Usnich: Institute of Neurogenetics, University of Luebeck, University Medical Center Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, Germany
Michael Wittig: Institute of Clinical Molecular Biology, Kiel University, 24105 Kiel, Germany
Christine Klein: Institute of Neurogenetics, University of Luebeck, University Medical Center Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, Germany
Inke R. König: Institute of Medical Biometry and Statistics, University of Luebeck, University Medical Center Schleswig-Holstein, Campus Luebeck, 23562 Luebeck, Germany
Katja Lohmann: Institute of Neurogenetics, University of Luebeck, University Medical Center Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, Germany
Michael Krawczak: Institute of Medical Informatics and Statistics, Kiel University, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany
Amke Caliebe: Institute of Medical Informatics and Statistics, Kiel University, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany

DOI: https://doi.org/10.3390/genes12121859
Journal volume & issue: Vol. 12, no. 12
p. 1859

Abstract

Read online

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.

Published in Genes

ISSN: 2073-4425 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General): Genetics
Website: http://www.mdpi.com/journal/genes/

About the journal

Abstract

Keywords