To establish the presence of a causal linkage between prevalent systemic diseases and keratoconus (KC).

Mendelian randomization (MR) analysis.

After an exhaustive screening process, genetic variants linked to various systemic diseases were identified as instrumental variables at the genome-wide significance level. Subsequently, MR analyses were conducted to elucidate their potential causal connection with KC (N = 26,742). The encompassed systemic ailments comprise diabetes, hay fever/allergic rhinitis/eczema, obstructive sleep apnea, thyroid dysfunction, aortic aneurysm, major depressive disorder, inflammatory bowel disease (including Crohn's disease and ulcerative colitis), and mitral valve prolapse. Our study adheres to the principles of Strengthening the Reporting of Observational Studies in Epidemiology Using MR guidelines.

Using inverse variance weighting as the primary MR analysis method, our findings revealed that hay fever/allergic rhinitis/eczema (odds ratio, 10.144; 95% CI, 2.441-42.149; P = .001) and ulcerative colitis (odds ratio, 1.147; 95% CI, 1.054-1.248; P = .002) were associated with an increased risk of KC within the largest population under scrutiny. Conversely, the prolonged hyperglycemic state did not exhibit a potentially protective effect in delaying the pathogenesis of KC, and no correlation was observed between the two (odds ratio, 0.320; 95% CI, 0.029-3.549; P = .353). Also, obstructive sleep apnea, thyroid function, aortic aneurysm, major depressive disorder, Crohn's disease, and mitral valve prolapse did not exhibit a causal association with KC (P > .05 for all comparisons).

This study indicates an increased risk of KC related to hay fever/allergic rhinitis/eczema and ulcerative colitis, with diabetes not providing a protective effect. These findings may potentially contribute some insights to inform clinical interventions.