Causal Relationship Between Common Allergic Diseases and Keratoconus: A Two-Sample Mendelian Randomization Study

Abstract

Purpose: To investigate the impact of several allergic diseases on the development of keratoconus (KC) from a genetic perspective. Methods: Data from multiple genome-wide association studies involving European ancestry individuals were used. Ultimately, 613 allergic conjunctivitis (AC) cases and 474,657 controls, 4387 allergic rhinitis (AR) cases and 471,273 controls, 4859 allergic asthma cases and 135,449 controls, 1169 allergic urticaria cases and 212,464 controls, 22,474 atopic dermatitis cases and 774,187 controls, and 311 KC cases and 209,287 controls were included. Then inverse-variance weighted (IVW) method, potential pleiotropy, heterogeneity, and leave-one-out analyses were assessed to investigate the causal effects of those allergic diseases on KC. Results: IVW estimates indicated that allergic asthma promoted the development of KC (IVW odds ratio [OR] = 2.18; 95% confidence interval [CI], 1.007–4.707; P = 0.048). However, the IVW estimates show that AC (IVW OR = 1.02; 95% CI, 0.960–1.086; P = 0.513), AR (OR = 0.26; 95% CI, 0.037–1.754; P = 0.165), atopic dermatitis (IVW OR = 1.50; 95% CI, 0.942–2.395; P = 0.088), allergic urticaria (IVW OR = 1.11; 95% CI, 0.822–1.511; P = 0.485) are not significantly causally associated with KC. Conclusions: Allergic asthma may promote KC by increasing allergy-related ocular inflammation. Translational Relevance: The possibility of increased KC in patients with allergic asthma should be considered.