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Assessing the role of polygenic background on the penetrance of monogenic forms in Parkinson\textquoterights disease. 2021.06.06.21253270
Hassanin, Emadeldin; May, Patrick; Aldisi, Rana et al.
2021
 

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Keywords :
Parkinson's disease; Polygenic risk; monogenic disease
Abstract :
[en] Background: Several rare and common variants are associated with Parkinson's disease. However, there is still an incomplete penetrance in the carriers of rare variants associated with Parkinson's disease. To address this issue, we investigated whether a PRS calculated from significant GWAS SNPs affects the penetrance of Parkinson's disease among carriers of rare monogenic variants in known Parkinson's disease genes and those with a family history. Methods: We calculated the PRS based on common variants and selected the carriers of rare monogenic variants by using the exome data from UK Biobank. Individuals were divided into three risk categories based on PRS: low (<10%), intermediate (10%-90%), and high (>90%) risk groups. We then compared how PRS affects Parkinson\textquoterights disease risk among carriers of rare monogenic variants and those with family-history. Results: We observed a two-fold higher odds ratio for a carrier of a monogenic variant that had a high PRS (OR 4.07,95\% CI, 1.72-8.08) compared to carriers with a low PRS (OR 1.91, 95\% CI, 0.31-6.05). In the same line, carriers with a first-degree family history and with \>90\% PRS have even a higher risk of developing PD (OR 23.53, 95\%CI 5.39-71.54) compared to those with \<90\% PRS (OR 9.54, 95\% CI 3.32-21.65). Conclusions: Our results show that PRS, carrier status, and family history contribute independently and additively to the Parkinson's disease risk.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
Disciplines :
Oncology
Author, co-author :
Hassanin, Emadeldin
May, Patrick  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Aldisi, Rana
Krawitz, Peter
Maj, Carlo
Bobbili, Dheeraj Reddy ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Language :
English
Title :
Assessing the role of polygenic background on the penetrance of monogenic forms in Parkinson\textquoterights disease. 2021.06.06.21253270
Publication date :
06 June 2021
Publisher :
Cold Spring Harbor Laboratory Press
Focus Area :
Systems Biomedicine
FnR Project :
FNR14429377 - Reduced Penetrance In Hereditary Movement Disorders: Elucidating Mechanisms Of Endogenous Disease Protection, 2020 (01/07/2020-30/06/2023) - Anne Grünewald
Funders :
The FNR supported P.M. as part of the National Centre of Excellence in Research on Parkinson's disease (NCER-PD, FNR11264123) and the DFG Research Units FOR2715 (INTER/DFG/17/11583046) and FOR2488 (INTER/DFG/19/14429377)
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