Journal Article

DZNE-2022-01291

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Mitochondrial and autophagy-lysosomal pathway polygenic risk scores predict Parkinson's disease.

Dehestani, M. (First author)DZNE* ; Liu, H.DZNE* ; Sreelatha, A. A. K. ; Schulte, C.DZNE* ; Bansal, V.DZNE* ; Gasser, T. (Last author)DZNE*

2022
Elsevier San Diego, Calif.

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Please use a persistent id in citations: doi:10.1016/j.mcn.2022.103751

Abstract: Polygenic Risk Scores (PRS), which allow assessing an individuals' genetic risk for a complex disease, are calculated as the weighted number of genetic risk alleles in an individual's genome, with the risk alleles and their weights typically derived from the results of genome-wide association studies (GWAS). Among a wide range of applications, PRS can be used to identify at-risk individuals and select them for further clinical follow-up. Pathway PRS are genetic scores based on single nucleotide polymorphisms (SNPs) assigned to genes involved in major disease pathways. The aim of this study is to assess the predictive utility of PRS models constructed based on SNPs corresponding to two cardinal pathways in Parkinson's disease (PD) including mitochondrial PRS (Mito PRS) and autophagy-lysosomal PRS (ALP PRS). PRS models were constructed using the clumping-and-thresholding method in a German population as prediction dataset that included 371 cases and 249 controls, using SNPs discovered by the most recent PD-GWAS. We showed that these pathway PRS significantly predict the PD status. Furthermore, we demonstrated that Mito PRS are significantly associated with later age of onset in PD patients. Our results may add to the accumulating evidence for the contribution of mitochondrial and autophagy-lysosomal pathways to PD risk and facilitate biologically relevant risk stratification of PD patients.

Keyword(s): Autophagy: genetics (MeSH) ; Genetic Predisposition to Disease (MeSH) ; Genome-Wide Association Study (MeSH) ; Humans (MeSH) ; Lysosomes (MeSH) ; Multifactorial Inheritance: genetics (MeSH) ; Parkinson Disease: genetics (MeSH) ; Polymorphism, Single Nucleotide (MeSH) ; Risk Factors (MeSH) ; Autophagy ; Lysosomal pathway ; Mitochondrial pathway ; Parkinson's disease ; Polygenic risk scores

Note: CC BY

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Contributing Institute(s):

1. Parkinson Genetics (AG Gasser)
2. Genome Biology of Neurodegenerative Diseases (AG Heutink 1)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Appears in the scientific report 2022

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