美国哥伦比亚大学Krzysztof Kiryluk团队利用全基因组多基因评分预测不同血统的慢性肾脏病。该研究于2022年6月16日在线发表于国际一流学术期刊《自然—医学》。

通过将APOL1风险基因型与肾脏功能的全基因组关联研究（GWAS）相结合，研究人员设计、优化并验证了慢性肾脏病（CKD）的全基因组多基因评分（GPS）。新的GPS在15个独立的队列中进行了测试，包括3个欧洲血统的队列（n=97,050），6个非洲血统的队列（n=14,544），4个亚洲血统的队列（n=8,625）和2个混血拉丁裔队列（n=3,625）。研究人员证明了分数的可转移性，在所有测试队列中都有可重复的表现。GPS的前2%与各血统的CKD风险增加近三倍有关。在非洲血统的队列中，APOL1风险基因型和GPS的多基因成分对CKD的风险有附加影响。

据了解，CKD是一种常见的复杂病症，与高发病率和死亡率有关。多基因预测可以加强CKD的筛查和预防；然而，这种方法还没有针对祖传的不同人群进行优化。

附：英文原文

Title: Genome-wide polygenic score to predict chronic kidney disease across ancestries

Author: Khan, Atlas, Turchin, Michael C., Patki, Amit, Srinivasasainagendra, Vinodh, Shang, Ning, Nadukuru, Rajiv, Jones, Alana C., Malolepsza, Edyta, Dikilitas, Ozan, Kullo, Iftikhar J., Schaid, Daniel J., Karlson, Elizabeth, Ge, Tian, Meigs, James B., Smoller, Jordan W., Lange, Christoph, Crosslin, David R., Jarvik, Gail P., Bhatraju, Pavan K., Hellwege, Jacklyn N., Chandler, Paulette, Torvik, Laura Rasmussen, Fedotov, Alex, Liu, Cong, Kachulis, Christopher, Lennon, Niall, Abul-Husn, Noura S., Cho, Judy H., Ionita-Laza, Iuliana, Gharavi, Ali G., Chung, Wendy K., Hripcsak, George, Weng, Chunhua, Nadkarni, Girish, Irvin, Marguerite R., Tiwari, Hemant K., Kenny, Eimear E., Limdi, Nita A., Kiryluk, Krzysztof

Issue&Volume: 2022-06-16

Abstract: 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.

DOI: 10.1038/s41591-022-01869-1

Source: https://www.nature.com/articles/s41591-022-01869-1