Association of genetic risk score and chronic kidney disease in a Japanese population
Association of genetic risk score and chronic kidney disease in a Japanese population
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DOI：
10.1111/nep.13479
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发表时间：
2019-06-01
期刊：
影响因子：
2.5
通讯作者：
Wakai, Kenji
中科院分区：
文献类型：
--
作者：
Fujii, Ryosuke;Hishida, Asahi;Wakai, Kenji
慢性肾脏疾病（CKD）是包括日本在内的世界范围内的公共卫生问题。最近的全基因组关联研究发现了CKD易感性变异。我们开发了一种基于CKD相关变异的遗传风险评分（GRS），并评估了GRS在日本人群中提高CKD患病率判别能力的可能性。本研究包括从日本12个多机构合作队列研究站点随机抽取的1283名参与者。结合在日本人群中发现的18个单核苷酸多态性构建了个体GRS。在本研究中，eGFR < 60 mL/min / 1.73 m(2)的参与者被定义为病例（3期CKD或更高）。采用Logistic回归分析检验GRS和CKD风险与性别、年龄、高血压和2型糖尿病之间的关系。CKD个体的发生率为8.3%，与之前报道的日本人群相比相对较低。在完全调整模型中，CKD的优势比为每10 GRS增量1.120(95%可信区间：1.042-1.203)（P = 0.002）。与未加GRS的模型相比，加GRS模型的c统计量显著增加（0.720 vs 0.719， p差= 0.008）。GRS的增加与CKD的风险增加有关。此外，GRS显著提高了日本人群CKD患病率的鉴别能力；然而，与非遗传性CKD危险因素相比，GRS带来的区分能力的提高似乎很小。
Chronic kidney disease (CKD) is a public health problem worldwide including Japan. Recent genome-wide association studies have discovered CKD susceptibility variants. We developed a genetic risk score (GRS) based on CKDassociated variants and assessed a possibility that the GRS can improve the discrimination capability for the prevalence of CKD in a Japanese population. The present study consists of 11 283 participants randomly selected from 12 Japan Multi-Institutional Collaborative Cohort Study sites. Individual GRS was constructed combining 18 single-nucleotide polymorphisms identified in a Japanese population. Participants with eGFR < 60 mL/min per 1.73 m(2) was defined as case (stage 3 CKD or higher) in this study. Logistic regression analysis was used to examine the association between the GRS and CKD risk with adjustment for sex, age, hypertension and type 2 diabetes mellitus. The frequency of individuals with CKD was 8.3%, which was relatively low compared with those previously reported in a Japanese population. The odds ratio of having CKD was 1.120 (95% confidence interval: 1.042-1.203) per 10 GRS increment in the fully adjusted model (P = 0.002). The C-statistic was significantly increased in the model with the GRS, comparing with the model without the GRS (0.720 vs 0.719, P-difference = 0.008). Increment of the GRS was associated with increased risk of CKD. Additionally, the GRS significantly improved the discriminatory ability of CKD prevalence in a Japanese population; however, the improvement of discriminatory ability brought about by the GRS seemed to be small compared with that of non-genetic CKD risk factors.