The genetic basis of dermatophytosis skin infection susceptibility

Dermatophytosis is a fungal infection affecting keratinized tissues such as skin, nails, and hair, presenting as red and itchy patches, nail thickening, or hair loss. It affects around 20% of the global population but the genetic architecture remains poorly understood. We performed a genome-wide association meta-analysis of over 250,000 cases and 1.37 million controls from FinnGen, Estonian Biobank, UK Biobank, and the Million Veteran Program and identified 30 genome-wide significant loci, including seven missense variants and two loci in high linkage disequilibrium with missense variants. Top associations were near ZNF646, HLA-DQB1, FLG, FTO, SLURP2, and KRT77. Additionally, dermatophytosis subtype analyses revealed 44 signals. Our results highlight the role of disrupted keratin biology, skin barrier defects, immune dysfunction, and obesity in dermatophytosis risk. We also observed genetic overlap with other skin conditions and obesity-related traits, providing insights into disease mechanisms and potential targets for prevention and treatment.