Polygenic prediction of keratoconus and its measures: cross-sectional and longitudinal analyses in community-based young adults

Samantha Sze-Yee Lee; Santiago Diaz-Torres; Weixiong He; Seyhan Yazar; Elsie Chan; Elaine W Chong; Puya Gharahkhani; Stuart MacGregor; Gareth Lingham; David A Mackey

doi:10.1016/j.ajo.2024.05.009

Polygenic prediction of keratoconus and its measures: cross-sectional and longitudinal analyses in community-based young adults

Am J Ophthalmol. 2024 May 11:S0002-9394(24)00211-3. doi: 10.1016/j.ajo.2024.05.009. Online ahead of print.

Authors

Affiliations

¹ University of Western Australia, Centre for Ophthalmology and Visual Science (incorporating the Lions Eye Institute), Perth, WA, Australia. Electronic address: samantha.sy.lee29@gmail.com.
² QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; Faculty of Medicine, University of Queensland, QLD, Australia.
³ University of Western Australia, Centre for Ophthalmology and Visual Science (incorporating the Lions Eye Institute), Perth, WA, Australia; Single Cell and Computational Genomics Laboratory, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
⁴ Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia.
⁵ Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia; Royal Melbourne Hospital, Melbourne, VIC, Australia.
⁶ QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; Faculty of Medicine, University of Queensland, QLD, Australia; School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
⁷ University of Western Australia, Centre for Ophthalmology and Visual Science (incorporating the Lions Eye Institute), Perth, WA, Australia; Centre for Eye Research Ireland, Environmental, Sustainability and Health Institute, Technological University Dublin, Dublin, Ireland.
⁸ University of Western Australia, Centre for Ophthalmology and Visual Science (incorporating the Lions Eye Institute), Perth, WA, Australia; Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, VIC, Australia; School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS, Australia.

PMID: 38740237
DOI: 10.1016/j.ajo.2024.05.009

Abstract

Aim: This study evaluates the performance of a multitrait polygenic risk score (PRS) in an independent cohort to predict incident or progression of keratoconus.

Design: Prospective cross-sectional and cohort study METHODS: Setting: Single-centre; Study population: 1,478 community-based young adults (18-30 years; 51% female), including 609 (52% female) who returned for an 8-year follow-up; Observation procedures: Scheimpflug imaging (Pentacam, Oculus), genotyping and development of a multitrait PRS previously validated to predict keratoconus in older adults.; Main outcome measure: Belin/Ambrόsio enhanced ectasia display (BAD-D) score and keratoconus, defined as BAD-D ≥2.6, were each analysed against the PRS using linear and logistic regression, respectively.

Results: Prevalence of keratoconus was 2.5% (95% confidence interval [CI]=1.9-3.6) in the cross-sectional cohort. Each z-score increase in PRS was associated with worse BAD-D z-score by 0.13 (95%CI= 0.08-0.18) and 1.6 increased odds of keratoconus. The 8-year keratoconus incidence was 2.6% (95%CI=1.3-4.0). Participants in the highest PRS decile were more likely to have incident keratoconus compared to the rest of the cohort (odds ratio= 3.85, 95%CI=1.21-12.22). For each z-score increase in PRS, 8-year change in BAD-D z-score worsened by 0.11 (95%CI=0.04 to 0.17).

Conclusion: A PRS for keratoconus could be useful in predicting incident keratoconus and progression, demonstrating its potential utility in clinical settings to identify patients at high risk of post-surgery ectasia or those who may benefit most from keratoconus intervention.

Keywords: genetics; keratoconus; polygenic risk; the Raine Study; young adults.