Genome-Wide Association Study of Staphylococcus aureus and Host Age in Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a chronic skin condition characterized by dry, itchy, and inflamed skin. It affects about 15% of children and 10% of adults around the world, decreasing quality of life. It is more common in young children, and presents differently with age: younger individuals experience more edema, while older individuals exhibit more desiccated lesions. The three etiologies of skin barrier dysfunction, immune dysregulation, and skin microbiome dysbiosis amplify each other through various molecular pathways, worsening disease symptoms and preventing recovery. In particular, colonization of the skin by Staphylococcus aureus is associated with disease severity and persistence. Previous studies have confirmed specific mechanisms of S. aureus modulation of the disease, but have not investigated how S. aureus gene content varies with age on AD patients. This study fills this gap by analyzing whole-genome sequencing data of 1584 S. aureus isolates previously cultured from young participants with AD. Results from microbial GWAS methods reveal that several S. aureus genes are differentially present in young children vs. adolescents with AD. One particularly strong association was found for saeS, which regulates gene expression of over 20 virulence factors related to AD. Future studies can build on these results to elucidate the clinical basis for AD age endotypes, and perhaps develop personalized therapies for AD patients, stratified by age.