Causal association of monocytes with chronic kidney disease and the mediation role of frailty: A study integrating large-scale two-sample Mendelian randomization and single-cell analysis
作者全名：Zhang, Cong; Deng, Jielian; Li, Kangjie; Lai, Guichuan; Liu, Hui; Zhang, Yuan; Zeng, Haijiao; Li, Wenlong; Zhong, Xiaoni; Wang, Yao; Xie, Biao
作者地址：[Zhang, Cong; Deng, Jielian; Li, Kangjie; Lai, Guichuan; Liu, Hui; Zhang, Yuan; Zeng, Haijiao; Li, Wenlong; Zhong, Xiaoni; Xie, Biao] Chongqing Med Univ, Sch Publ Hlth, Dept Epidemiol & Hlth Stat, Yixue Rd, Chongqing 400016, Peoples R China; [Wang, Yao] Yidu Cloud Beijing Technol Co Ltd, Beijing, Peoples R China
通信作者：Zhong, XN; Xie, B (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Dept Epidemiol & Hlth Stat, Yixue Rd, Chongqing 400016, Peoples R China.; Wang, Y (通讯作者)，Yidu Cloud Beijing Technol Co Ltd, Beijing, Peoples R China.
来源：ARCHIVES OF GERONTOLOGY AND GERIATRICS
ESI学科分类：CLINICAL MEDICINE
WOS号：WOS:001226351000001
JCR分区：Q2
影响因子：3.5
年份：2024
卷号：123
期号：
开始页：
结束页：
文献类型：Article
关键词：Frailty; Chronic kidney disease; Monocyte; Mendelian randomization; Single -cell
摘要：Background: Recent research reported that frailty was prevalent among adults with chronic kidney disease (CKD) in clinical trials, and monocytes illustrated a similar difference in these two diseases compared to the normal. However, the scientific evidence for a causal relationship between these two diseases was lacking, with further exploration into whether monocytes co-regulate them. Methods: We aimed to integrate large-scale Mendelian randomization (MR) and single-cell transcriptome analysis to determine whether there was a causal relationship between frailty and CKD (Bidirectional two-sample Mendelian determined the causal direction), whether monocytes impacted them, and whether the two diseases shared genetic variation sites. Based on 441 Genome-wide association study datasets, this study utilized five MR methods, multiple sensitivity analysis, and corresponding single-cell transcriptome datasets as proof. Results: The association between frailty and CKD was significantly causal, and frailty increased the risk of CKD in patients (OR (95 %CI): 3.5597 (1.8369-6.8982), p = 0.000168909). The exposure monocyte can increase the risk of frailty and CKD in patients, especially with high expression of HLA genes in these cells. The existing twosample MR results cannot reject the hypothesis that monocytes increase the risk of CKD by inducing frailty. rs9275271' 1mb genetic location above and below had been proven to be an effective genetic space for both frailty and CKD. Conclusion: We conducted the largest MR to date on frailty, monocyte, and CKD, and found a significant causal association between frailty and CKD, with the single-cell analysis confirmed. The exposure monocytes increased the risk of frailty and CKD, particularly with high expression of HLA genes in these cells. We identified a potential common genetic variant space, rs9275271, associated with frailty and CKD, providing insights into the genetic basis of these conditions.
基金机构：National Youth Science Foundation Project [82204159]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202300423]
基金资助正文：This research was funded by (National Youth Science Foundation Project) , grant number [82204159] ) and Science and Technology Research Program of Chongqing Municipal Education Commission (Grant No. KJQN202300423) .
