Genome-wide association study of the risk of chronic kidney disease and kidney-related traits in the Japanese population: J-Kidney-Biobank
Genome-wide association study of the risk of chronic kidney disease and kidney-related traits in the Japanese population: J-Kidney-Biobank
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DOI：
10.1038/s10038-022-01094-1
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发表时间：
2022-11
影响因子：
3.5
通讯作者：
Y. Sugawara;Y. Hirakawa;H. Nagasu;A. Narita;A. Katayama;J. Wada;M. Shimizu;T. Wada;H. Kitamura;T. Nakano;H. Yokoi;M. Yanagita;S. Goto;I. Narita;S. Koshiba;G. Tamiya;M. Nangaku;Masayuki Yamamoto;N. Kashihara
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文献类型：
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作者：
Y. Sugawara;Y. Hirakawa;H. Nagasu;A. Narita;A. Katayama;J. Wada;M. Shimizu;T. Wada;H. Kitamura;T. Nakano;H. Yokoi;M. Yanagita;S. Goto;I. Narita;S. Koshiba;G. Tamiya;M. Nangaku;Masayuki Yamamoto;N. Kashihara
慢性肾脏病（CKD）是一种以肾功能逐渐丧失伴肾小球滤过率（eGFR）估计值降低为特征的综合征，可能伴有尿白蛋白/肌酐比值（UACR）升高。尽管已经对肾脏相关性状进行了跨种族全基因组关联研究（GWAS），但在日本人群中很少进行分析，尤其是UACR性状。在这项研究中，我们进行了GWAS，以确定日本人的多个肾脏相关性状相关的基因座。首先，为了检测与CKD、eGFR和UACR相关的基因座，我们对以下两个数据集进行了单独的GWAS：在七所大学医院诊断的475例CKD病例和3471例健康受试者（数据集1），以及3664例eGFR <60 ml/min/1.73 m2或尿蛋白≥ 1+的CKD疑似个体和5952例健康受试者（数据集2）。其次，我们在这两个数据集之间进行了荟萃分析，并检测了以下相关基因座：10个CKD基因座，9个eGFR基因座和22个UACR基因座。其中22个基因座为首次报道。CKD的显著基因座中有一半与eGFR的基因座相同，而与UACR相关的大多数基因座与CKD或eGFR相关的基因座不同。日本人群的GWAS发现了以前未检测到的新遗传成分。结果还表明，主要以UACR增加为特征的组具有与eGFR降低为特征的组不同的遗传特征。
Chronic kidney disease (CKD) is a syndrome characterized by a gradual loss of kidney function with decreased estimated glomerular filtration rate (eGFR), which may be accompanied by an increase in the urine albumin-to-creatinine ratio (UACR). Although trans-ethnic genome-wide association studies (GWASs) have been conducted for kidney-related traits, there have been few analyses in the Japanese population, especially for the UACR trait. In this study, we conducted a GWAS to identify loci related to multiple kidney-related traits in Japanese individuals. First, to detect loci associated with CKD, eGFR, and UACR, we performed separate GWASs with the following two datasets: 475 cases of CKD diagnosed at seven university hospitals and 3471 healthy subjects (dataset 1) and 3664 cases of CKD-suspected individuals with eGFR <60 ml/min/1.73 m2or urinary protein ≥ 1+ and 5952 healthy subjects (dataset 2). Second, we performed a meta-analysis between these two datasets and detected the following associated loci: 10 loci for CKD, 9 loci for eGFR, and 22 loci for UACR. Among the loci detected, 22 have never been reported previously. Half of the significant loci for CKD were shared with those for eGFR, whereas most of the loci associated with UACR were different from those associated with CKD or eGFR. The GWAS of the Japanese population identified novel genetic components that were not previously detected. The results also suggest that the group primarily characterized by increased UACR possessed genetically different features from the group characterized by decreased eGFR.