Association of atopic dermatitis with conjunctivitis and other ocular surface diseases: A bidirectional two-sample Mendelian randomization study.

Abstract

Observational studies have suggested associations of atopic dermatitis (AD) with conjunctivitis and other ocular surface diseases (OSDs). It is still unclear, however, whether or in which direction causal relationships exist, because these associations could be confounded. Our study aims to examine the causal association of AD with conjunctivitis and other OSDs. A bidirectional two-sample Mendelian randomization (MR) study was performed with genome-wide association study (GWAS) summary-level statistics. Genetic instruments for AD from a GWAS meta-analysis study conducted by the EArly Genetics & Lifecourse Epidemiology eczema consortium were used to investigate AD's relationships to conjunctivitis and other OSDs among cases from the FinnGen consortium. Genetic correlations were calculated using linkage disequilibrium score regression. Causal estimates were derived by the inverse-variance weighted method and were verified through a series of sensitivity analyses. Genetically predicted AD linked to higher risk of conjunctivitis (OR, 1.48; 95% CI, 1.33-1.65; p=8.65 × 10-13 ) and allergic conjunctivitis (OR, 1.53; 95%CI, 1.31-1.77; p=3.77 × 10-8 ), as well as atopic conjunctivitis (OR, 1.76; 95%CI, 1.24-2.52; p=1.76 × 10-3 ). Additionally, suggestive causal effects of AD on chronic conjunctivitis (OR, 1.76; 95%CI, 1.24-2.52; p=5.78 × 10-3 ) and keratitis (OR, 1.14; 95%CI, 1.01-1.30; p=3.58 × 10-2 ) were found. No significant causal effect of AD was identified in relation to keratitis, keratoconus and pterygium. Concerning the reverse directions, no significant associations were noted. Findings of this MR study support a causal effect between AD and conjunctivitis, but not vice versa. These findings have clinical implications for the management of AD and conjunctivitis.