Susceptibility genes for allergic conjunctivitis revealed by cross-tissue transcriptome-wide association study

Allergic conjunctivitis (AC) is a common immune-mediated ocular disorder, characterized by clinical manifestations such as ocular itching, conjunctival hyperemia, lacrimation, and mucoid discharge, which significantly impair patients' visual function and quality of life. Despite extensive research efforts devoted to uncovering the genetic predisposition to AC, the underlying pathogenic genes and molecular mechanisms remain incompletely understood, necessitating further research to elucidate its genetic basis. This study utilized AC data from the FinnGen R12 and incorporated expression quantitative trait loci data in the Genotype-Tissue Expression v8 database to perform a cross-tissue transcriptome-wide association study (TWAS). Analytical methods included functional summary-based imputation (FUSION), unified test for molecular signatures (UTMOST), and gene analysis combined with multi-marker genome annotation (MAGMA). To further validate the results, Mendelian randomization (MR) analysis and colocalization analysis were performed. Through TWAS and MAGMA analyses, 13 susceptibility genes associated with AC were identified. Following MR and colocalization analyses, three candidate genes—GAL3ST2, PDCD1 and TLR6—were ultimately selected and validated by FUMA tool, which may influence progression of AC by regulating pathways related to Toll-like receptor signaling. In conclusion, three susceptibility genes linked to the risk of AC were identified, providing new insights into the genetic mechanisms and potential pathogenic pathways underlying AC.