Chronic kidney disease (CKD) is a common complex condition associated with high morbidity and mortality. Polygenic prediction could enhance CKD screening and prevention; however, this approach has not been optimized for ancestrally diverse populations. By combining APOL1 risk genotypes with genome-wide association studies (GWAS) of kidney function, we designed, optimized and validated a genome-wide polygenic score (GPS) for CKD. The new GPS was tested in 15 independent cohorts, including 3 cohorts of European ancestry (n = 97,050), 6 cohorts of African ancestry (n = 14,544), 4 cohorts of Asian ancestry (n = 8,625) and 2 admixed Latinx cohorts (n = 3,625). We demonstrated score transferability with reproducible performance across all tested cohorts. The top 2% of the GPS was associated with nearly threefold increased risk of CKD across ancestries. In African ancestry cohorts, the APOL1 risk genotype and polygenic component of the GPS had additive effects on the risk of CKD.

慢性肾脏病（CKD）是一种常见的复杂疾病，发病率和死亡率很高。多基因预测可以加强 CKD 筛查和预防；然而，这种方法尚未针对祖先多样化的人群进行优化。通过将APOL1风险基因型与肾功能全基因组关联研究 (GWAS) 相结合，我们设计、优化和验证了 CKD 的全基因组多基因评分 (GPS)。新的 GPS 在 15 个独立队列中进行了测试，其中包括 3 个欧洲血统队列 ( n = 97,050)、6 个非洲血统队列 ( n = 14,544)、4 个亚洲血统队列 ( n = 8,625) 和 2 个混合拉丁裔队列 ( n = 14,544)。 = 3,625）。我们在所有测试组中证明了分数可转移性和可重复的表现。 GPS 中前 2% 的人与不同血统的 CKD 风险增加近三倍相关。在非洲血统队列中， APOL1风险基因型和 GPS 的多基因成分对 CKD 风险具有累加效应。