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

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

28 Citations (Scopus)

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 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.

Original language	English
Journal	Genes
Volume	12
Issue number	12
ISSN	2073-4425
DOIs	https://doi.org/10.3390/genes12121859
Publication status	Published - 23.11.2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being
SDG 10 Reduced Inequalities

Research Areas and Centers

Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
Research Area: Medical Genetics

DFG Research Classification Scheme

2.23-06 Molecular and Cellular Neurology and Neuropathology

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10.3390/genes12121859

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Koch, S., Laabs, B.-H., Kasten, M., Vollstedt, E.-J., Becktepe, J., Brüggemann, N., Franke, A., Krämer, U. M., Kuhlenbäumer, G., Lieb, W., Mollenhauer, B., Neis, M., Trenkwalder, C., Schäffer, E., Usnich, T., Wittig, M., Klein, C., König, I. R., Lohmann, K., ... Caliebe, A. (2021). Validity and Prognostic Value of a Polygenic Risk Score for Parkinson's Disease. Genes, 12(12). https://doi.org/10.3390/genes12121859

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title = "Validity and Prognostic Value of a Polygenic Risk Score for Parkinson's Disease",

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 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.",

author = "Sebastian Koch and Bj{\"o}rn-Hergen Laabs and Meike Kasten and Eva-Juliane Vollstedt and Jos Becktepe and Norbert Br{\"u}ggemann and Andre Franke and Kr{\"a}mer, \{Ulrike M\} and Gregor Kuhlenb{\"a}umer and Wolfgang Lieb and Brit Mollenhauer and Miriam Neis and Claudia Trenkwalder and Eva Sch{\"a}ffer and Tatiana Usnich and Michael Wittig and Christine Klein and K{\"o}nig, \{Inke R\} and Katja Lohmann and Michael Krawczak and Amke Caliebe",

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Koch, S, Laabs, B-H , Kasten, M , Vollstedt, E-J, Becktepe, J, Brüggemann, N, Franke, A, Krämer, UM, Kuhlenbäumer, G, Lieb, W, Mollenhauer, B, Neis, M, Trenkwalder, C, Schäffer, E, Usnich, T, Wittig, M, Klein, C , König, IR , Lohmann, K, Krawczak, M & Caliebe, A 2021, 'Validity and Prognostic Value of a Polygenic Risk Score for Parkinson's Disease', Genes, vol. 12, no. 12. https://doi.org/10.3390/genes12121859

TY - JOUR

T1 - Validity and Prognostic Value of a Polygenic Risk Score for Parkinson's Disease

AU - Koch, Sebastian

AU - Laabs, Björn-Hergen

AU - Kasten, Meike

AU - Vollstedt, Eva-Juliane

AU - Becktepe, Jos

AU - Brüggemann, Norbert

AU - Franke, Andre

AU - Krämer, Ulrike M

AU - Kuhlenbäumer, Gregor

AU - Lieb, Wolfgang

AU - Mollenhauer, Brit

AU - Neis, Miriam

AU - Trenkwalder, Claudia

AU - Schäffer, Eva

AU - Usnich, Tatiana

AU - Wittig, Michael

AU - Klein, Christine

AU - König, Inke R

AU - Lohmann, Katja

AU - Krawczak, Michael

AU - Caliebe, Amke

PY - 2021/11/23

Y1 - 2021/11/23

N2 - 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.

AB - 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.

U2 - 10.3390/genes12121859

DO - 10.3390/genes12121859

M3 - Journal articles

C2 - 34946808

SN - 2073-4425

VL - 12

JO - Genes

JF - Genes

IS - 12

ER -

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

Abstract

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Research Areas and Centers

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