Abstract：
OBJECTIVE: This study evaluates the performance of a multitrait polygenic risk score (PRS) in an independent cohort to predict incident or progression of keratoconus.
METHODS: Prospective cross-sectional and cohort study METHODS: Setting: Single-center; Study population: 1478 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 analyzed 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 = 0.04-0.17).
CONCLUSIONS: 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 postsurgery ectasia or those who may benefit most from keratoconus intervention.
METHODS: Prospective cross-sectional and cohort study METHODS: Setting: Single-center; Study population: 1478 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 analyzed 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 = 0.04-0.17).
CONCLUSIONS: 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 postsurgery ectasia or those who may benefit most from keratoconus intervention.
摘要：
目的：本研究评估了多性状多基因风险评分（PRS）在独立队列中预测圆锥角膜事件或进展的表现。
方法：前瞻性横断面和队列研究方法：设置：单中心；研究人群：1,478名基于社区的年轻人（18-30岁；51％为女性），包括609名（52％的女性）返回进行8年随访；观察程序：Scheimpflug成像（Pentacam，Oculus),先前验证的多性状PRS的基因分型和发展可预测老年人的圆锥角膜。；主要结局指标：贝林/阿姆布鲁西奥增强扩张显示（BAD-D）评分和圆锥角膜，定义为BAD-D≥2.6，分别使用线性和逻辑回归分析PRS，分别。
结果：横断面队列中圆锥角膜的患病率为2.5%（95%置信区间[CI]=1.9-3.6）。PRS的z得分增加与BAD-Dz得分差相关，增加0.13（95CI=0.08-0.18），圆锥角膜的几率增加1.6。8年圆锥角膜发病率为2.6%(95CI=1.3-4.0)。与其他队列相比，PRS分位数最高的参与者更有可能发生圆锥角膜（比值比=3.85，95CI=1.21-12.22）。对于PRS的每一个z分数增加，BAD-Dz评分的8年变化恶化了0.11（95CI=0.04至0.17）。
结论：圆锥角膜的PRS可用于预测圆锥角膜的发生和进展，证明其在临床环境中的潜在效用，以识别术后扩张的高风险患者或可能从圆锥角膜干预中受益最大的患者。
方法：前瞻性横断面和队列研究方法：设置：单中心；研究人群：1,478名基于社区的年轻人（18-30岁；51％为女性），包括609名（52％的女性）返回进行8年随访；观察程序：Scheimpflug成像（Pentacam，Oculus),先前验证的多性状PRS的基因分型和发展可预测老年人的圆锥角膜。；主要结局指标：贝林/阿姆布鲁西奥增强扩张显示（BAD-D）评分和圆锥角膜，定义为BAD-D≥2.6，分别使用线性和逻辑回归分析PRS，分别。
结果：横断面队列中圆锥角膜的患病率为2.5%（95%置信区间[CI]=1.9-3.6）。PRS的z得分增加与BAD-Dz得分差相关，增加0.13（95CI=0.08-0.18），圆锥角膜的几率增加1.6。8年圆锥角膜发病率为2.6%(95CI=1.3-4.0)。与其他队列相比，PRS分位数最高的参与者更有可能发生圆锥角膜（比值比=3.85，95CI=1.21-12.22）。对于PRS的每一个z分数增加，BAD-Dz评分的8年变化恶化了0.11（95CI=0.04至0.17）。
结论：圆锥角膜的PRS可用于预测圆锥角膜的发生和进展，证明其在临床环境中的潜在效用，以识别术后扩张的高风险患者或可能从圆锥角膜干预中受益最大的患者。
