UNASSIGNED: To assess whether a PRS improves prediction of POAG onset in patients with ocular hypertension.
UNASSIGNED: This was a post hoc analysis of the Ocular Hypertension Treatment Study. Data were collected from 22 US sites with a mean (SD) follow-up of 14.0 (6.9) years. A total of 1636 participants were followed up from February 1994 to December 2008; 1077 participants were enrolled in an ancillary genetics study, of which 1009 met criteria for this analysis. PRS was calculated using summary statistics from the largest cross-ancestry POAG meta-analysis, with weights trained using 8 813 496 variants from 449 186 cross-ancestry participants in the UK Biobank. Data were analyzed from July 2022 to December 2023.
UNASSIGNED: From February 1994 to June 2002, participants were randomized to either topical intraocular pressure-lowering medication or close observation. After June 2002, both groups received medication.
UNASSIGNED: Outcome measures were hazard ratios for POAG onset. Concordance index and time-dependent areas under the receiver operating characteristic curve were used to compare the predictive performance of multivariable Cox proportional hazards models.
UNASSIGNED: Of 1009 included participants, 562 (55.7%) were female, and the mean (SD) age was 55.9 (9.3) years. The mean (SD) PRS was significantly higher for 350 POAG converters (0.24 [0.95]) compared with 659 nonconverters (-0.12 [1.00]) (P < .001). POAG risk increased 1.36% (95% CI, 1.08-1.64) with each higher PRS decile, with conversion ranging from 9.52% (95% CI, 7.09-11.95) in the lowest PRS decile to 21.81% (95% CI, 19.37-24.25) in the highest decile. Comparison of low-risk and high-risk PRS tertiles showed a 2.0-fold increase in 20-year POAG risk for participants of European and African ancestries. In the subgroup randomized to delayed treatment, each increase in PRS decile was associated with a 0.52-year (95% CI, 0.01-1.03) decrease in age at diagnosis (P = .047). No significant linear association between PRS and age at POAG diagnosis was present in the early treatment group. Prediction models significantly improved with the addition of PRS as a covariate (C index = 0.77) compared with the Ocular Hypertension Treatment Study baseline model (C index = 0.75) (P < .001). Each 1-SD higher PRS conferred a mean hazard ratio of 1.25 (95% CI, 1.13-1.44) for POAG onset.
UNASSIGNED: Higher PRS was associated with increased risk for POAG in patients with ocular hypertension. The inclusion of a PRS improved the prediction of POAG onset.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT00000125.
■评估PRS是否改善了高眼压患者POAG发病的预测。
■这是对眼部高血压治疗研究的事后分析。数据来自22个美国站点,平均(SD)随访14.0(6.9)年。从1994年2月至2008年12月,共对1636名参与者进行了随访;1077名参与者参加了一项辅助遗传学研究,其中1009符合此分析的标准。PRS是使用来自最大的交叉血统POAG荟萃分析的汇总统计数据计算的,使用来自英国生物库449186名交叉祖先参与者的8813496种变体进行体重训练。数据从2022年7月到2023年12月进行了分析。
从1994年2月到2002年6月,参与者被随机分配到局部眼压降低药物或密切观察。2002年6月后,两组均接受药物治疗。
■结果测量是POAG发作的危险比。使用一致性指数和受试者工作特征曲线下的时间依赖性面积来比较多变量Cox比例风险模型的预测性能。
■在1009名参与者中,562(55.7%)为女性,平均(SD)年龄为55.9(9.3)岁。350个POAG转化者的平均(SD)PRS(0.24[0.95])明显高于659个非转化者(-0.12[1.00])(P<.001)。POAG风险增加1.36%(95%CI,1.08-1.64),每提高PRS分位数,转化率从最低PRS分位数的9.52%(95%CI,7.09-11.95)到最高分位数的21.81%(95%CI,19.37-24.25)。低风险和高风险PRS三元组的比较显示,欧洲和非洲祖先的参与者20年POAG风险增加了2.0倍。在随机分组延迟治疗的亚组中,PRS每增加1分位数,与诊断时0.52岁(95%CI,0.01-1.03)的年龄减少相关(P=.047).在早期治疗组中,PRS与POAG诊断时的年龄之间没有显着的线性关联。与高血压治疗研究基线模型(C指数=0.75)相比,PRS作为协变量(C指数=0.77)的预测模型显着改善(P<0.001)。每1-SD较高的PRS赋予POAG发作的平均风险比为1.25(95%CI,1.13-1.44)。
■高PRS与高眼压患者POAG风险增加相关。包含PRS改善了POAG发作的预测。
■ClinicalTrials.gov标识符:NCT00000125。