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

Eye volume 39, pages 1508–1516 (2025)Cite this article

Subjects

A Correction to this article was published on 03 April 2025

This article has been updated

Abstract

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.

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Fig. 1: AMD PRS in the study cohort.
Fig. 2: Discriminatory power of classifying participants with increased RIT versus rest of cohort.

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Change history

  • 27 March 2025

    The original online version of this article was revised: In this article the article title has been updated to “Polygenic Risk Score Impact Visual Function in Healthy: The Northern Ireland Sensory Ageing Study” because of inoccret grammar/missing words.

  • 03 April 2025

    A Correction to this paper has been published: https://doi.org/10.1038/s41433-025-03773-7

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Funding

Atlantic Philanthropies, the Economic and Social Research Council, the UKCRC Centre of Excellence for Public Health Northern Ireland, the Centre for Ageing Research and Development in Ireland, the Office of the First Minister and Deputy First Minister, the Health and Social Care Research and Development Division of the Public Health Agency, the Wellcome Trust/Wolfson Foundation, Fight for Sight (Ref No.: 1906), and Queen’s University Belfast provide core financial support for the Northern Ireland Cohort of Longitudinal Study of Ageing study. The authors alone are responsible for the interpretation of the data, and any views or opinions presented are solely those of the authors and do not necessarily represent those of the Northern Ireland Cohort of Longitudinal Study of Ageing study team. The Northern Ireland Sensory Ageing study was funded by grants from the College of Optometrists, Diabetes UK, Macular Society, RNIB, Guide Dogs for the Blind, Thomas Pocklington Trust and the Belfast Association for the Blind. Role of the Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Institute of Ophthalmology, University College London, London, UK

    Fangyao Tang & Sobha Sivaprasad

  2. Centre for Public Health, Queen’s University Belfast, Belfast, UK

    Ruth E. Hogg, David M. Wright & Laura Smyth

  3. Optometry and Vision Sciences, City, University of London, London, UK

    Bethany E. Higgins

  4. National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital National Health Service Foundation Trust, London, UK

    Sobha Sivaprasad

Authors
  1. Fangyao Tang
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  2. Ruth E. Hogg
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  3. Bethany E. Higgins
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  4. David M. Wright
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Contributions

SS, REH: research design. FYT: data analysis, interpretation, REH, BEH, DMW, LS: research execution. All authors contributed towards the preparation of the manuscript and approved the final submitted version. The corresponding author is solely responsible for managing communication between co-authors; that all authors are included in the author list; order has been agreed by all authors; and that all authors are aware that the paper was submitted.

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Correspondence to Sobha Sivaprasad.

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SS is a member of the Eye editorial board.

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The original online version of this article was revised: In this article the article title has been updated to “Polygenic Risk Score Impact Visual Function in Healthy: The Northern Ireland Sensory Ageing Study” because of inoccret grammar/missing words.

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Tang, F., Hogg, R.E., Higgins, B.E. et al. Polygenic Risk Score Impact on Visual Function in Older Individuals with Healthy Macula: The Northern Ireland Sensory Ageing Study. Eye 39, 1508–1516 (2025). https://doi.org/10.1038/s41433-025-03642-3

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