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

Zied Landoulsi; Katja Lohmann; Eva Juliane Vollstedt; Emily Wedgwood-Benn; Lisa Marie Niestroj; Björn Hergen Laabs; Sebastian Sendel; Alexander Balck; Max Borsche; Dennis Lal; Anne Grünewald; Norbert Brüggemann; Andre Franke; Andrew Hicks; Meike Kasten; Kirsten E. Zeuner; Lara M. Lange; Wolfgang Lieb; Brit Mollenhauer; Heike Pawlack; Peter P. Pramstaller; Amke Caliebe; Inke R. König; Patrick May; Christine Klein

doi:10.1038/s41531-025-01076-y

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

Zied Landoulsi^*, Katja Lohmann, Eva Juliane Vollstedt, Emily Wedgwood-Benn, Lisa Marie Niestroj, Björn Hergen Laabs, Sebastian Sendel, Alexander Balck, Max Borsche, Dennis Lal, Anne Grünewald, Norbert Brüggemann, Andre Franke, Andrew Hicks, Meike Kasten, Kirsten E. Zeuner, Lara M. Lange, Wolfgang Lieb, Brit Mollenhauer, Heike PawlackPeter P. Pramstaller, Amke Caliebe, Inke R. König, Patrick May, Christine Klein

^*Corresponding author for this work

Transversal Translational Medicine

Research output: Contribution to journal › Article › Research › peer-review

Abstract

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.

Original language	English
Article number	225
Number of pages	7
Journal	npj Parkinson's Disease
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41531-025-01076-y
Publication status	Published - 1 Aug 2025

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Landoulsi, Z., Lohmann, K., Vollstedt, E. J., Wedgwood-Benn, E., Niestroj, L. M., Laabs, B. H., Sendel, S., Balck, A., Borsche, M., Lal, D., Grünewald, A., Brüggemann, N., Franke, A., Hicks, A., Kasten, M., Zeuner, K. E., Lange, L. M., Lieb, W., Mollenhauer, B., ... Klein, C. (2025). Large-scale copy number variant analysis in genes linked to Parkinson´s disease. npj Parkinson's Disease, 11(1), Article 225. https://doi.org/10.1038/s41531-025-01076-y

@article{328706493abd4c0eb927cf6a39f8a789,

title = "Large-scale copy number variant analysis in genes linked to Parkinson´s disease",

abstract = "Genetic studies of Parkinson{\textquoteright}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.",

author = "Zied Landoulsi and Katja Lohmann and Vollstedt, \{Eva Juliane\} and Emily Wedgwood-Benn and Niestroj, \{Lisa Marie\} and Laabs, \{Bj{\"o}rn Hergen\} and Sebastian Sendel and Alexander Balck and Max Borsche and Dennis Lal and Anne Gr{\"u}newald and Norbert Br{\"u}ggemann and Andre Franke and Andrew Hicks and Meike Kasten and Zeuner, \{Kirsten E.\} and Lange, \{Lara M.\} and Wolfgang Lieb and Brit Mollenhauer and Heike Pawlack and Pramstaller, \{Peter P.\} and Amke Caliebe and K{\"o}nig, \{Inke R.\} and Patrick May and Christine Klein",

note = "Funding: This study was supported by the German Research Foundation (DFG, project FOR 2488). Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = aug,

day = "1",

doi = "10.1038/s41531-025-01076-y",

language = "English",

volume = "11",

journal = "npj Parkinson's Disease",

issn = "2373-8057",

publisher = "Springer Nature",

number = "1",

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Landoulsi, Z, Lohmann, K, Vollstedt, EJ, Wedgwood-Benn, E, Niestroj, LM, Laabs, BH, Sendel, S, Balck, A, Borsche, M, Lal, D, Grünewald, A, Brüggemann, N, Franke, A, Hicks, A, Kasten, M, Zeuner, KE, Lange, LM, Lieb, W, Mollenhauer, B, Pawlack, H, Pramstaller, PP, Caliebe, A, König, IR, May, P & Klein, C 2025, 'Large-scale copy number variant analysis in genes linked to Parkinson´s disease', npj Parkinson's Disease, vol. 11, no. 1, 225. https://doi.org/10.1038/s41531-025-01076-y

TY - JOUR

T1 - Large-scale copy number variant analysis in genes linked to Parkinson´s disease

AU - Landoulsi, Zied

AU - Lohmann, Katja

AU - Vollstedt, Eva Juliane

AU - Wedgwood-Benn, Emily

AU - Niestroj, Lisa Marie

AU - Laabs, Björn Hergen

AU - Sendel, Sebastian

AU - Balck, Alexander

AU - Borsche, Max

AU - Lal, Dennis

AU - Grünewald, Anne

AU - Brüggemann, Norbert

AU - Franke, Andre

AU - Hicks, Andrew

AU - Kasten, Meike

AU - Zeuner, Kirsten E.

AU - Lange, Lara M.

AU - Lieb, Wolfgang

AU - Mollenhauer, Brit

AU - Pawlack, Heike

AU - Pramstaller, Peter P.

AU - Caliebe, Amke

AU - König, Inke R.

AU - May, Patrick

AU - Klein, Christine

PY - 2025/8/1

Y1 - 2025/8/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105012386799

UR - https://pubmed.ncbi.nlm.nih.gov/40750593/

U2 - 10.1038/s41531-025-01076-y

DO - 10.1038/s41531-025-01076-y

M3 - Article

C2 - 40750593

AN - SCOPUS:105012386799

SN - 2373-8057

VL - 11

JO - npj Parkinson's Disease

JF - npj Parkinson's Disease

IS - 1

M1 - 225

ER -

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

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