Genome-wide association study of copy number variations in Parkinson’s disease
- the Global Parkinson Genetics Program (GP2),
- Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson’s Disease (COURAGE-PD) consortium,
- Zied Landoulsi(corresponding author)(Author),
- Ashwin Ashok Kumar Sreelatha(Author),
- Nicole Kuznetsov(Author),
- Claudia Schulte(Author)
- Luxembourg Institute of Health,
- University of Luxembourg,
- University of Tuebingen,
- National Institute on Aging (NIA),
- DataTecnica LLC,
- Hertie Institute for Clinical Brain Research
Open access
Publication Information
Output type
Original language
EnglishArticle number
160Journal (Volume, Issue Number)
npj Parkinson's Disease (Volume 12, Issue 1)Publication milestones
- Published - 12/2026
Publication status
Publication IDs
- Scopus: 105043709422
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.