Unraveling the Link Between Obesity and Keratoconus Risk Based on Genetic Evidence.

PURPOSE: Keratoconus (KCN) is a progressive corneal disorder leading to vision impairment. While genetic and environmental factors contribute to its development, the role of obesity in KCN risk remains unclear. This study aimed to estimate the causal effect between obesity, measured by body mass index (BMI) and waist-to-hip ratio (WHR), and the risk of KCN.

METHODS

This two-sample Mendelian randomization (MR) case-control study used genome-wide association study data from GIANT, MRC-IEU UK Biobank, and FinnGen. BMI and WHR were used to estimate general and central obesity, respectively. Data from 311 KCN cases and 209,287 controls were analyzed. Causal effect estimates of BMI, WHR, and obesity-related chronic diseases on KCN risk were calculated.

RESULTS

Genetically predicted higher BMI was significantly associated with increased KCN risk (odds ratio [OR] = 2.003; 95% confidence interval [CI], 1.203-3.335; P = 0.008), as determined using European genetic databases. Consistent results were observed with the weighted median, MR-Egger, and MR-pleiotropy residual sum and outlier methods. No significant causal effect was found between WHR and KCN risk (OR = 0.578; 95% CI, 0.196-1.705; P = 0.321). Sensitivity analyses showed no evidence of pleiotropy, and no significant causal effect was observed between obesity-related chronic diseases and KCN risk.

CONCLUSIONS

Using European genetic databases, general obesity was identified as a strong, independent causal effect contributor to KCN, while central obesity showed no association. These findings provide new insights into obesity's role in KCN development and may inform future preventive strategies.

TRANSLATIONAL RELEVANCE: This study suggests that general obesity is a causal risk factor for keratoconus, suggesting that obesity management could help prevent or mitigate KCN progression.