Genome-wide association study of copy number variations in Parkinson’s disease

Landoulsi, Zied, Sreelatha, Ashwin Ashok Kumar, Kuznetsov, Nicole, Schulte, Claudia, Bobbili, Dheeraj Reddy, Williams, Nigel ORCID: https://orcid.org/0000-0003-1177-6931 and Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483 2026. Genome-wide association study of copy number variations in Parkinson’s disease. npj Parkinson's Disease 12 , 160. 10.1038/s41531-025-01245-z

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Abstract

We investigated the role of copy number variations (CNVs) in Parkinson’s disease (PD) using genotyping data from 10,815 patients (2731 early-onset PD, EOPD) and 8901 controls from the COURAGE-PD consortium. CNVs were analyzed using a sliding window genome-wide association and burden approach. No genome-wide significant CNVs were detected in the overall cohort, but a robust deletion spanning exons 2–6 of PRKN was identified in EOPD cases, validated by MLPA, and replicated in the GP2 dataset (23,089 cases, 18,824 controls). CNV burden was significantly enriched in PD-related genes, primarily driven by PRKN, with the strongest effect observed in EOPD. PRKN CNV carriers showed earlier age at onset, confirmed by survival analysis. No association was observed for genome-wide or large CNV burden. Our findings reinforce the pivotal role of PRKN deletions in early-onset PD and highlight the need for high-resolution CNV analysis in large cohorts to uncover additional rare contributors to PD risk.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Additional Information:	Full author list available at DOI
Publisher:	Nature Research
Date of First Compliant Deposit:	20 July 2026
Date of Acceptance:	16 December 2025
Last Modified:	20 Jul 2026 13:34
URI:	https://orca.cardiff.ac.uk/id/eprint/188341

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