| Title: |
Genome-wide association study of copy number variations in Parkinson's disease. |
| Authors: |
Landoulsi, Zied; Sreelatha, Ashwin Ashok Kumar; Schulte, Claudia; Bobbili, Dheeraj Reddy; Montanucci, Ludovica; Leu, Costin; Niestroj, Lisa-Marie; Hassanin, Emadeldin; Domenighetti, Cloé; Pavelka, Lukas; Sugier, Pierre-Emmanuel; Radivojkov-Blagojevic, Milena; Lichtner, Peter; Portugal, Berta; Edsall, Connor; Kruger, Jens; Hernandez, Dena G.; Blauwendraat, Cornelis; Mellick, George D.; Zimprich, Alexander; Pirker, Walter; Tan, Manuela; Rogaeva, Ekaterina; Lang, Anthony E.; Koks, Sulev; Taba, Pille; Lesage, Suzanne; Brice, Alexis; Corvol, Jean-Christophe; Chartier-Harlin, Marie-Christine; Mutez, Eugenie; Brockmann, Kathrin; Deutschländer, Angela B.; Hadjigeorgiou, Georges M.; Dardiotis, Efthimos; Stefanis, Leonidas; Simitsi, Athina Maria; Valente, Enza Maria; Petrucci, Simona; Straniero, Letizia; Zecchinelli, Anna; Pezzoli, Gianni; Brighina, Laura; Ferrarese, Carlo; Annesi, Grazia; Quattrone, Andrea; Gagliardi, Monica; Burbulla, Lena F.; Matsuo, Hirotaka; Nakayama, Akiyoshi; Hattori, Nobutaka; Nishioka, Kenya; Chung, Sun Ju; Kim, Yun Joong; Kolber, Pierre; van de Warrenburg, Bart Pc; Bloem, Bastiaan R.; Singleton, Andrew B.; Toft, Mathias; Pihlstrom, Lasse; Guedes, Leonor Correia; Ferreira, Joaquim J.; Bardien, Soraya; Carr, Jonathan; Tolosa, Eduardo; Ezquerra, Mario; Pastor, Pau; Wirdefeldt, Karin; Pedersen, Nancy L.; Ran, Caroline; Belin, Andrea C.; Puschmann, Andreas; Clarke, Carl E.; Morrison, Karen E.; Krainc, Dimitri; Farrer, Matt J.; Lal, Dennis; Elbaz, Alexis; Gasser, Thomas; Krüger, Rejko; Sharma, Manu; May, Patrick |
| Contributors: |
Centre de recherche en épidémiologie et santé des populations (CESP); Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse; GHU AP-HP. Université Paris Saclay-GHU AP-HP. Université Paris Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay; UFR Sciences de la santé Simone Veil (UVSQ Santé); Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay; Sorbonne Université (SU); Institut du Cerveau = Paris Brain Institute (ICM); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS); Lille Neurosciences & Cognition - U 1172 (LilNCog); Institut Pasteur de Lille; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); This study used data from the Courage-PD consortium, conducted under a partnership agreement among 35 studies. The Courage-PD consortium is supported by the EU Joint Program for Neurodegenerative Disease research (JPND https://neurodegenerationresearch.eu). P. May was funded by the Fonds National de Recherche (FNR), Luxembourg, as part of the National Centre of Excellence in Research on Parkinsons Disease (NCER-PD, FNR11264123). Z. Landoulsi and P. May were supported by the DFG Research Unit FOR2715 (INTER/DFG/17/ 11583046), FOR2488 (INTER/DFG/19/14429377) and the National Centre for Excellence in Research on Parkinsons disease (NCER-PD). A.B. Singleton, D.G. Hernandez, and C. Edsall are funded by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services, project ZO1 AG000949. E. Rogaeva is funded by the Canadian Consortium on Neurodegeneration in Aging. S.Koks is funded by MSWA. P. Taba is the recipient of an Estonian Research Council Grant PRG957. E.M.Valente is funded by the Italian Ministry of Health (Ricerca Corrente 2021). S. Bardien and J. Carr are supported by grants from the National Research Foundation of South Africa (grant number: 106052); the South African Medical Research Council (Self-Initiated Research Grant); and Stellenbosch University, South Africa; they also acknowledge the support of the NRF-DST Centre of Excellence for Biomedical Tuberculosis Research; South African Medical Research Council Centre for Tuberculosis Research; and Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town. P. Pastor have received funding from the Spanish Ministry of Science and Innovation (SAF2013-47939-R). K. Wirdefeldt and N.L. Pedersen are funded by the Swedish Research Council, grant numbers K2002-27X-14056-02B, 521-2010-2479, 521-2013-2488, and 2017-02175. N.L. Pedersen is funded by the National Institutes of Health, grant numbers ES10758 and AG 08724. C. Ran is funded by the Marta Lundkvist Foundation, Swedish Brain Foundation, and Karolinska Institutet Research Fund. A.C. Belin is funded by the Swedish Brain Foundation, Swedish Research Council, and Karolinska Institutet Research Funds. M. Tan is funded by the Parkinson's UK. M. Sharma was supported by grants from the German Research Council (DFG/SH 599/6-1), MSA Coalition, and The Michael J. Fox Foundation (USA Genetic Diversity in PD Program: GAP-India Grant ID: 17473). A. Elbaz reports grants from Agence nationale de recherche (ANR), The Michael J. Fox Foundation, Plan Ecophyto (French Ministry of Agriculture), and France Parkinson outside the submitted work. PG GEN sample collection was funded by the MRC and UK Medical Research Council (C.E. Clarke and K.E. Morrison). The sponsors had no role in the study design, data collection, data analysis, data interpretation, writing of the report, or decision to submit the paper for publication. |
| Source: |
https://lilloa.hal.science/hal-04987814 ; 2025. |
| Publisher Information: |
CCSD |
| Publication Year: |
2025 |
| Collection: |
Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; Objective: To investigate the impact of copy number variations (CNVs) on Parkinson's disease (PD) pathogenesis using genome-wide data and explore their role in sporadic PD. Methods: We analyzed CNV data from 11,035 PD patients (including 2,731 early-onset PD (EOPD)) and 8,901 controls from the COURAGE-PD consortium using a sliding window CNV-GWAS and genome-wide burden analysis. The independent dataset from the Global Parkinson Genetics Program (GP2) consisted of 23,089 cases and 18,824 controls were used to validate our initial findings. Results: The exploratory dataset identifies multiple CNV regions associated with PD risk. The nominated CNV loci were not confirmed in an independent dataset, except that only a deletion in the PRKN gene, a well-established EOPD locus, remained genome-wide significant and robustly supported. CNV burden analysis showed a higher prevalence of CNVs in PD-related genes in patients compared to controls (OR=1.56 [1.18-2.09], p=0.0013), with PRKN showing the highest burden (OR=1.47 [1.10-1.98], p=0.026). Patients with CNVs in PRKN had an earlier disease onset. Burden analysis with controls and EOPD patients showed similar results. Interpretation: The largest CNV-based GWAS on PD highlights both the promise and pitfalls of array-based CNV detection in PD and underscores the relevance of whole-genome sequencing approaches in resolving the role of CNV in PD. The array-based findings are prone towards false positive findings that might arise either from platform limitations and/or cohort biases. Future studies require improved genotyping resolution and rigorous cross-cohort validation to reliably assess CNV contributions to PD risk. |
| Document Type: |
report |
| Language: |
French |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/39228715; PUBMED: 39228715 |
| DOI: |
10.1101/2024.08.21.24311915 |
| Availability: |
https://lilloa.hal.science/hal-04987814; https://lilloa.hal.science/hal-04987814v1/document; https://lilloa.hal.science/hal-04987814v1/file/2024.08.21.24311915v1.full.pdf; https://doi.org/10.1101/2024.08.21.24311915 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.CECAE0E6 |
| Database: |
BASE |