Genetic liability to higher frailty index may increase the risk of ophthalmic disease

Frailty and age-related eye diseases are common in older people; however, whether there is a causal link remains unknown. We aimed to explore the causal associations between the frailty index (FI) and ophthalmic traits and identify modifiable mediators.

Linkage disequilibrium score regression and two-sample Mendelian randomization were applied to identify genetic correlations and causal associations between FI and ophthalmic traits. Summary data for FI was obtained from a genome-wide association study that included 175,226 individuals of European ancestry. Summary-level statistics for ophthalmic traits were obtained from relative GWASs. Summary-level data for cardiovascular risk factors, inflammatory biomarkers, and the central nervous system were used to identify the possible mediators.

FI had a significant genetic correlation with 10 ophthalmic traits. Per SD increment of FI, the odds ratio was 1.329 (95% CI, 1.123, 1.573; P = 9.5 × 10^-4) for cataracts, 1.825 (95% CI, 1.115, 2.986; P = 0.016) for keratitis, 1.798 (95% CI, 1.039, 3.11; P = 0.036) for disorders of vitreous body and 1.478 (95% CI, 1.005, 2.173; P = 0.046) for disorders of sclera, cornea, iris and ciliary body. The MR effect estimates of FI on ophthalmic traits were attenuated after adjusting for mental disorders, type 2 diabetes, triglyceride, and interleukin-8 (IL-8) levels.

This study reports a genetic correlation and causal association between FI and ophthalmic traits, in which mental disorders, type 2 diabetes, triglycerides, and IL-8 may play a mediating role. These findings highlight a possible method to reduce the risk of FI-related ophthalmic diseases.