s improved with the use of race-free eGFR. Background CKD is a risk factor of cardiovascular disease and early death. Recently, polygenic risk scores (PRSs) have been developed to quantify risk for CKD. However, African ancestry populations are underrepresented in both CKD genetic studies and PRS development overall. Moreover, European ancestry–derived PRSs demonstrate diminished predictive performance in African ancestry populations. Methods This study aimed to develop a PRS for CKD in Black American populations. We obtained score weights from a meta-analysis of genome-wide association studies for eGFR in the Million Veteran Program and Reasons for Geographic and Racial Differences in Stroke Study to develop an eGFR PRS. We optimized the PRS risk model in a cohort of participants from the Hypertension Genetic Epidemiology Network. Validation was performed in subsets of Black participants of the Trans-Omics in Precision Medicine Consortium and Genetics of Hypertension Associated Treatment Study. Results The prevalence of CKD—defined as stage 3 or higher—was associated with the PRS as a continuous predictor (odds ratio [95% confidence interval]: 1.35 [1.08 to 1.68]) and in a threshold-dependent manner. Furthermore, including APOL1 risk status—a putative variant for CKD with higher prevalence among those of sub-Saharan African descent—improved the score's accuracy. PRS associations were robust to sensitivity analyses accounting for traditional CKD risk factors, as well as CKD classification based on prior eGFR equations. Compared with previously published PRS, the predictive performance of our PRS was comparable with a European ancestry–derived PRS for kidney traits. However, single-ancestry PRSs were less predictive than multi-ancestry–derived PRSs. Conclusions In this study, we developed a PRS that was significantly associated with CKD with improved predictive accuracy when including APOL1 risk status. However, PRS generated from multi-ancestry populations outperformed single-ancestry PRS in our study....

中文翻译：

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美国黑人人群 CKD 的单血统与多血统多基因风险评分


s 通过使用无种族 eGFR 而得到改善。背景 CKD 是心血管疾病和早期死亡的危险因素。最近，已经开发了多基因风险评分 （PRS） 来量化 CKD 的风险。然而，非洲血统人群在 CKD 遗传研究和 PRS 发展总体上代表性不足。此外，欧洲血统衍生的 PRS 在非洲血统人群中的预测性能降低。方法 本研究旨在开发美国黑人人群 CKD 的 PRS。我们从百万退伍军人计划和中风研究中地理和种族差异的原因研究中获得了 eGFR 全基因组关联研究的荟萃分析，以开发 eGFR PRS。我们在来自高血压遗传流行病学网络的一组参与者中优化了 PRS 风险模型。在精准医学跨组学联盟和高血压遗传学相关治疗研究的黑人参与者亚群中进行了验证。结果 CKD 的患病率（定义为 3 期或更高阶段）与 PRS 作为连续预测因子 （比值比 [95% 置信区间] ： 1.35 [1.08 至 1.68]）相关，并且以阈值依赖性方式。此外，包括 APOL1 风险状态（一种推定的 CKD 变体，在撒哈拉以南非洲血统人群中患病率更高）提高了评分的准确性。PRS 关联对于考虑传统 CKD 危险因素的敏感性分析以及基于先前 eGFR 方程的 CKD 分类是稳健的。与以前发表的 PRS 相比，我们的 PRS 对肾脏特征的预测性能与欧洲血统衍生的 PRS 相当。然而，单血统 PRS 的预测性低于多血统衍生的 PRS。 结论 在这项研究中，我们开发了一种与 CKD 显著相关的 PRS，当包括 APOL1 风险状态时，预测准确性更高。然而，在我们的研究中，由多血统人群产生的 PRS 优于单血统 PRS。