Polygenic Risk Score Impact on Visual Function in Older Individuals with Healthy Macula: The Northern Ireland Sensory Ageing Study.

Background/objectives: Although polygenic risk scores (PRSs) have been developed for age-related macular degeneration (AMD), it is not known whether these scores are associated with impairment of visual functions in older individuals with healthy macula. We evaluated age-related changes in visual function in people aged 55 years or above with healthy macula and determined the associations of age-related visual function changes with AMD PRS in people with healthy macula.

Subjects/methods: Participants aged 55 years or above with healthy macula and a comparative group of people with early or intermediate AMD from the Northern Ireland Sensory Ageing study were included. 45 SNPs were included for PRS calculation.

Results: A total of 470 participants with healthy macula were included (Beckman grade 0 or 1). The comparator group consisted of participants with early AMD (n = 87) or intermediate AMD (n = 48). All visual functions except metrics of central visual field assessment showed a significant decline with age in adjusted linear regression models. Rod intercept time (RIT) was the only visual function significantly associated with PRS with Beta = 0.12 (95% confidence interval: 0.01-0.23), P = 0.03. A PRS integrated model achieved the highest area under the receiver operating characteristic curve (AUC) of 0.803 (0.732 to 0.874) to distinguish between normal or increased RIT.

Conclusions and relevance: We observed a significant decline in multiple visual functions with increasing age. However, PRS was significantly associated with RIT only, highlighting the genetic association of age-related decline in rod function.