Identification of Treatment Targets in Allergic Conjunctivitis Through Proteome-Scale Mendelian Randomization...

Allergic conjunctivitis (AC) is a condition with a rising prevalence that occasionally leads to irreversible visual impairment. However, few novel therapeutic targets have been identified for AC. The investigation aims to utilize the Mendelian randomization (MR) technique to explore the causal impacts exerted by the plasma proteome on AC.

An evaluation was conducted on a two-sample MR study utilizing 2,940 plasma proteins from the UK Biobank Pharma Proteomics Project (UKB-PPP) to investigate their causal links with AC. Confirmation of these MR results was achieved using Summary-data-based MR (SMR) and Bayesian colocalization techniques. Moreover, evaluations concerning the druggability of proteins, interactions among proteins, and phenome-wide MR (Phe-MR) studies were conducted to ascertain the functionalities of the identified proteins implicated in causality.

MR analysis identified five circulating proteins (TLR1, ING1, RALY, CSF2, and ITGAM) whose genetically predicted plasma levels were significantly associated with AC risk (P _FDR < 0.05). Functional enrichment analysis of the identified proteins revealed statistically significant biologically relevant pathways, including macrophage activation and pathways of plasma membrane signaling receptor complex, suggesting underlying immune and receptor-mediated mechanisms in AC. SMR and HEIDI validation supports four (TLR1, ING1, ITGAM, and CSF2) of five MR-identified proteins as causal candidates for AC. Subsequent colocalization analysis provided further support for two credible proteins (ING1 and CSF2). Protein druggability suggests CSF2 and ING1 as novel and potentially druggable candidates for AC.

Our research identified proteins that appear to have causal effects and could serve as potential therapeutic targets for AC.