Genetic Evidence Supporting a Causal Role of Snoring in Keratoconus: A Bidirectional Mendelian Randomization Study

Purpose: To clarify the controversial causal association between snoring and keratoconus (KCN), which is crucial in clinical prevention and treatment. Methods: This is a 2-sample bidirectional mendelian randomization (MR) case–control study. MR is an innovative method that uses genetic variation as a natural experiment to investigate the causal relationships between potentially modifiable risk factors and health outcomes in observational data. The single nucleotide polymorphisms associated with snoring were retrieved from the UK biobank cohort with 218,346 participants (61,792 cases and 156,554 controls). The summary statistics of KCN were obtained from the European ancestry with 209,598 subjects (311 cases and 209,287 controls). The inverse-variance-weighted method was applied as the primary estimate, whereas weighted median and MR-pleiotropy residual sum and outlier played a subsidiary role. Results: Elevated risk of snoring showed a robust causal effect on KCN (inverse-variance-weighted: causal effect = 9.821, 95% confidence interval [CI], 1.944–17.699, P = 0.015), which was consistent with complementary methods of the weighted median (causal effect = 11.117, 95% CI, 2.603–19.631, P = 0.010), maximum likelihood (causal effect = 10.245, 95% CI, 3.967–16.523, P = 0.001), and MR-pleiotropy residual sum and outlier (causal effect = 9.793, 95% CI, 2.316–17.269, P = 0.028). However, there was no causality of KCN on the increasing risk of snoring. Conclusions: This study provides genetic evidence supporting the causal role of snoring on KCN. Our findings provide new insights into potential strategies to manage KCN.