Characterization of genetic loci associated with allergic conjunctivitis

Despite the high prevalence of allergic conjunctivitis, the genetic factors contributing to it have not been characterized in detail.

We sought to characterize genetic factors associated with allergic conjunctivitis both in relation to and independent of systemic atopic or allergic conditions.

We performed a genome-wide association study meta-analysis using data from FinnGen, Estonian Biobank, and UK Biobank cohorts. A total of 45,734 cases with allergic conjunctivitis and 1,084,159 controls were included. We conducted a phenome-wide association study and pathway and enrichment analyses, and assessed genetic correlations with other phenotypes.

Genome-wide significant (P < 5 × 10^-8) associations were identified for allergic conjunctivitis at 34 loci, many of which had not been reported to associate with allergic conjunctivitis before. Many of the associated loci included genes involved in immunology and allergy-related conditions, for example, ID2 and TSLP. Several loci were also associated with other allergic health conditions, such as asthma, allergic rhinitis, and eczema. Three loci (EIF2AK2, RANBP2, and NFAT5) had no previous association with allergy-related phenotypes. We detected that allergic conjunctivitis is associated with pathways related to neuroinflammation, immune responses, and cytokine signaling. We detected an enrichment of genes associated with immune-related biological processes such as cytokine production. Allergic conjunctivitis was genetically correlated with 27 phenotypes.

We identified 34 allergic conjunctivitis-associated loci, most of which were involved in immunology and allergy-related conditions. Our findings underline the central role of inflammation-related genes in genetic predisposition to allergic conjunctivitis and advance the overall understanding of its genetic background.