Genetics; Copy number variation; Parkinson's disease
Abstract :
[en] Genetic studies of Parkinson's disease (PD) have focused on single nucleotide variants (SNVs), with limited attention to copy number variants (CNVs). This study investigates CNVs in PD using candidate PD-related genes and genome-wide approaches. We identified CNVs from the ProtectMove project genotyping data of 2364 PD patients and 2909 controls using PennCNV. We validated 119 of 137 detected CNVs in PD-related genes (87%) using MLPA/qPCR, including 104 in PRKN, six in PARK7, four in SNCA, and others in LRRK2, RAB32, and VPS35. CNVs were present in 2.4% of patients and 1.5% of controls. Notably, 0.9% of patients carried potentially disease-causing CNVs compared to 0.1% in controls. CNVs were enriched in patients (OR = 1.67, p = 0.03) due to PRKN CNVs, particularly in early-onset cases. These results highlight the importance of CNVs in PD, particularly in PRKN, and suggest that rare CNVs in LRRK2 and RAB32 may contribute to disease risk and diagnostic potential.
Research center :
Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) Luxembourg Centre for Systems Biomedicine (LCSB): Molecular & Functional Neurobiology (Grünewald Group)
Disciplines :
Genetics & genetic processes Neurology
Author, co-author :
LANDOULSI, Zied ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine > Bioinformatics Core > Research BioCore ; Luxembourg Institute of Health, Strassen, Luxembourg. zied.landoulsi@lih.lu
Lohmann, Katja; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany
Vollstedt, Eva-Juliane; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany
Wedgwood-Benn, Emily; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany
Niestroj, Lisa-Marie; Cologne Center for Genomics (CCG), Medical Faculty of the University of Cologne, Cologne, Germany
Laabs, Björn-Hergen; Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany
Sendel, Sebastian; Institute of Medical Informatics and Statistics, Christian-Albrechts-University of Kiel, University Hospital Schleswig-Holstein, Kiel, Germany
Balck, Alexander; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany ; Department of Neurology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
Borsche, Max; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany ; Department of Neurology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
Lal, Dennis; Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA ; Epilepsy Center, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA ; Stanley Center for Psychiatric Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
GRÜNEWALD, Anne ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Molecular and Functional Neurobiology
Brüggemann, Norbert; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany ; Department of Neurology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
Franke, Andre; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany
Hicks, Andrew; Institute for Biomedicine, Eurac Research, Bolzano, Italy
Kasten, Meike; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany ; Department of Psychiatry, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
Zeuner, Kirsten E; Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Lange, Lara M; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany ; Department of Neurology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
Lieb, Wolfgang; Institute of Epidemiology, Christian-Albrechts-University of Kiel, Kiel, Germany
Mollenhauer, Brit; Paracelsus Elena Clinic, Kassel, Germany ; Department of Neurology, University Medical Center, Georg August University, Göttingen, Germany
Pawlack, Heike; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany
Pramstaller, Peter P; Institute for Biomedicine, Eurac Research, Bolzano, Italy
Caliebe, Amke; Institute of Medical Informatics and Statistics, Christian-Albrechts-University of Kiel, University Hospital Schleswig-Holstein, Kiel, Germany
König, Inke R; Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany
MAY, Patrick ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core
Klein, Christine; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany
FNR14429377 - ProtectMove II - Reduced Penetrance In Hereditary Movement Disorders: Elucidating Mechanisms Of Endogenous Disease Protection, 2020 (01/07/2020-30/06/2023) - Anne Grünewald
Name of the research project :
R-AGR-3877 - INTER/DFG/19/14429377 ProtectMove II - GRÜNEWALD Anne
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