Association between polygenic risk for schizophrenia and retinal morphology: A cross-sectional analysis of the United Kingdom Biobank.

We examined the relationship between genetic risk for schizophrenia (SZ), using polygenic risk scores (PRSs), and retinal morphological alterations. Retinal structural and vascular indices derived from optical coherence tomography (OCT) and color fundus photography (CFP) and PRSs for SZ were analyzed in N = 35,024 individuals from the prospective cohort study, United Kingdom Biobank (UKB). Results indicated that macular ganglion cell-inner plexiform layer (mGC-IPL) thickness was significantly inversely related to PRS for SZ, and this relationship was strongest within higher PRS quintiles and independent of potential confounders and age. PRS, however, was unrelated to retinal vascular characteristics, with the exception of venular tortuosity, and other retinal structural indices (macular retinal nerve fiber layer [mRNFL], inner nuclear layer [INL], cup-to-disc ratio [CDR]). Additionally, the association between greater PRS and reduced mGC-IPL thickness was only significant for participants in the 40-49 and 50-59 age groups, not those in the 60-69 age group. These findings suggest that mGC-IPL thinning is associated with a genetic predisposition to SZ and may reflect neurodevelopmental and/or neurodegenerative processes inherent to SZ. Retinal microvasculature alterations, however, may be secondary consequences of SZ and do not appear to be associated with a genetic predisposition to SZ.