Large-scale copy number variant analysis in genes linked to Parkinson´s disease

• Published in: NPJ Parkinson's Disease Vol. 11; no. 1; pp. 225 - 7
• Main Authors: Landoulsi, Zied, Lohmann, Katja, Vollstedt, Eva-Juliane, Wedgwood-Benn, Emily, Niestroj, Lisa-Marie, Laabs, Björn-Hergen, Sendel, Sebastian, Balck, Alexander, Borsche, Max, Lal, Dennis, Grünewald, Anne, Brüggemann, Norbert, Franke, Andre, Hicks, Andrew, Kasten, Meike, Zeuner, Kirsten E., Lange, Lara M., Lieb, Wolfgang, Mollenhauer, Brit, Pawlack, Heike, Pramstaller, Peter P., Caliebe, Amke, König, Inke R., May, Patrick, Klein, Christine
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208; 692/617/375/1718; Biomedical and Life Sciences; Biomedicine; Genes; Genomes; Health risk assessment; Neurology; Neurosciences; Parkinson's disease; Patients
• ISSN: 2373-8057; 2373-8057
• DOI: 10.1038/s41531-025-01076-y

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.