GENETICS OF ATOPIC DERMATITIS IN THE SINGAPORE AND MALAYSIA CHINESE

Abstract

Atopic dermatitis (AD) is a chronic, itchy, and inflammatory skin condition associated with elevated immunoglobulin E levels. We conducted a genome-wide association study (GWAS) on Chinese populations in Singapore and Malaysia, identifying genetic factors associated with AD. Four associations were functionally characterized. Inflammation was found to be promoted through reduced autophagy levels, in the case of the aquaporin 3 gene, or by modulating nuclear factor kappa B activity, in the case of the ubiquitin D gene. A deep intronic genetic variant was also found to regulate tight junction protein 2 gene expression levels through methylation, influencing epidermal hyperplasia. Predictions also suggest identified long non-coding RNA variants may implicate interleukin-27 production and type 1 interferon signalling. Our GWAS-identified AD-associated variants were also found to have high AD genomic risk prediction ability. Understanding these genetic influences enhances our comprehension of the disease, aiding advancements in diagnosis, treatment, and management.