AbstractRetinal nerve fibre layer (RNFL) thickness has been associated with cognitive function but it is unclear whether RNFL thinning is secondary to cortical loss, or if the same disease process affects both. We explored whether there is phenotypic sharing between RNFL thickness and cognitive traits and whether such sharing is due to genetic factors. Detailed eye and cognitive examination were performed on 1602 twins (mean age: 56.4 years; range: 18–89) from the TwinsUK cohort. Associations between RNFL thickness and ophthalmic, cognitive and other predictors were assessed using linear regression or analysis of variance models. Heritability analyses were performed using uni- and bivariate Cholesky decomposition models. RNFL was thinner with increase in myopia and with decrease in disc area (p < 0.001). A thicker RNFL was associated with better performance on mini mental state examination (MMSE, F(5,883) = 5.8, p < 0.001) and with faster reaction time (RT, β = −0.01; p = 0.01); independent of the effects of age, refractive error and disc area (p < 0.05). RNFL thickness was highly heritable (82%) but there was low phenotypic sharing between RNFL thickness and MMSE (5%, 95% CI: 0–10%) or RT (7%, 95% CI: 1–12%). This sharing, however, was mostly due to additive genetic effects (67% and 92% of the shared variance respectively).