biostudies-literatureUnknown117Wang J<h4>Background</h4>Loss of Y chromosome (LOY), an age-related somatic mutation, is associated with various age-related diseases, but its role in the onset and progression of Parkinson's disease (PD) remains unclear. This study investigated the relationship between blood LOY levels and the risk of PD onset and progression.<h4>Methods</h4>We estimated the LOY level for each male participant based on genome-wide arrays or whole genome sequencing data. We performed Cox proportional hazards regression analysis among 222,598 male participants in the UK Biobank and linear mixed model analysis involving 2574 male individuals with PD across 14 cohorts, encompassing 19,562 visits. In the Parkinson's Progression Markers Initiative (PPMI) cohort, we further compared brain structure using T1-weighted mEBioMedicine105769https://www.ebi.ac.uk/biostudies/studies/S-EPMC12159889biostudies-literatureImpact of Y chromosome loss on the risk of Parkinson's disease and progression.PMC12159889Scherzer CRDong Xvan Hilten JJDu WLesage SWang JTysnes OBWills AMAlves GMaiti BValentino RRLocascio JJKoks SHayes MTHung AYChen XGrowdon JHLiao ZLiao YBrice AShoulson IHeutink PCampbell MCTaba PMangone GKasten MMaple-Grodem JWilliams-Gray CHKlein CLin CSchwarzschild MAMarinus JPerlmutter JSInternational Genetics of Parkinson Disease Progression (IGPP) ConsortiumCormier-Dequaire FMollenhauer BCorvol JCTrenkwalder CElbaz AHerrington TMSchwarzchild MABeach TGBarker RALiu GRavian BfalseImpact of Y chromosome loss on the risk of Parkinson's disease and progression.<h4>Background</h4>Loss of Y chromosome (LOY), an age-related somatic mutation, is associated with various age-related diseases, but its role in the onset and progression of Parkinson's disease (PD) remains unclear. This study investigated the relationship between blood LOY levels and the risk of PD onset and progression.<h4>Methods</h4>We estimated the LOY level for each male participant based on genome-wide arrays or whole genome sequencing data. We performed Cox proportional hazards regression analysis among 222,598 male participants in the UK Biobank and linear mixed model analysis involving 2574 male individuals with PD across 14 cohorts, encompassing 19,562 visits. In the Parkinson's Progression Markers Initiative (PPMI) cohort, we further compared brain structure using T1-weighted m2025-01-01T00:00:00Z2025 Jul2026-06-06T15:12:02.717Z2026-06-01T03:10:57.039ZS-EPMC121598894044640110.1016/j.ebiom.2025.105769