Genetics-informed new causal proteins in atopic dermatitis pathogenesis and treatment

Abstract

Atopic dermatitis (AD) is an immune-related skin disease with a genetic background. Numerous loci have been identified associated with AD to better comprehend its complicated genetic mechanisms by genome‑wide association studies (GWASs). However, current studies reveal the underlying mechanisms of these loci in the pathogenesis of AD inadequately. To explore the plasma proteins genetically correlated with AD via the GWAS data. Herein, we adopted recent AD GWAS data (N = 796,661) and the dataset of plasma protein quantitative trait loci (pQTLs), comprising 1,348 proteins from individuals of European descent. We first conducted the AD-related proteome-wide association studies (PWASs) (N = 7,213) by integrating pQTLs with the AD GWAS statistics and identified six significant plasma proteins by PWAS (P < 0.05). Then, the potential causal proteins of AD were identified via Mendelian randomization (MR), and four causal proteins of AD were discovered afterward. Following this, Bayesian colocalization analysis then explored proteins sharing the same causal variants. Three causal proteins strongly associated with the pathogenesis of AD were eventually pinpointed. Finally, we discovered drugs that could be repurposed for AD with the plasma proteins that might contribute to the pathogenesis of AD in the Drug Gene Interaction Database.