Association of haematopoietic mosaic loss of chromosome Y with dermatitis and eczema risk: an analysis in a large-scale prospective cohort study

BACKGROUND: Evidence regarding the role of hematopoietic mosaic loss of chromosome Y (mLOY) in incident dermatitis and eczema (DE) risk, and its contribution to male susceptibility remains limited. OBJECTIVE: To evaluate the associations of mLOY with incident DE and to assess whether mLOY may contribute to sex differences in DE susceptibility. METHODS: This prospective study included 189,572 UK Biobank men free of DE at baseline, recruited between 2006 and 2010. Hematopoietic mLOY was derived from genotyping intensity data and analysed as both categorical mLOY status and continuous mLOY percentage (mLOY%). Cox proportional hazards models were used to estimate associations with incident DE. Sex susceptibility was evaluated in a 1:1 propensity score-matched male-female cohort. Genetic modification was assessed using a DE polygenic risk score (PRS), and mediation by circulating metabolites was explored in the Metabolomics analyses. RESULTS: During follow-up, 9,608 men developed DE. In fully adjusted models, both low mLOY (8-20%) and high mLOY (>20%) were associated with increased DE risk, with the strongest association observed for high mLOY [adjusted hazard ratio (aHR) 1.44, 95% CI 1.26-1.66; P