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

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.

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