Kidney damage causally affects the brain cortical structure: A Mendelian randomization study.
Kidney damage causally affects the brain cortical structure: A Mendelian randomization study.
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DOI：
10.1016/j.ebiom.2021.103592
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发表时间：
2021-10
期刊：
影响因子：
11.1
通讯作者：
Lin T
中科院分区：
文献类型：
--
作者：
Chen X;Kong J;Pan J;Huang K;Zhou W;Diao X;Cai J;Zheng J;Yang X;Xie W;Yu H;Li J;Pei L;Dong W;Qin H;Huang J;Lin T
慢性肾脏病（CKD）患者的大脑皮质结构发生了变化，但其原因尚未确定。在此，我们使用孟德尔随机化（MR）来揭示肾损伤对大脑皮质结构的因果关系。来自CKDGen联盟的480，698名参与者的估计肾小球滤过率（eGFR）的全基因组关联研究总结数据用于确定遗传预测的eGFR。来自CKDGen Consortium的567，460名个体的数据用于评估基因决定的CKD;来自英国生物库的302，687名参与者用于评估基因预测的白蛋白尿。此外，来自ENIGMA Consortium的51，665例患者的数据用于评估遗传易感性与eGFR降低、CKD和进行性白蛋白尿与大脑皮质厚度（TH）或脑顶区（SA）改变之间的关系。磁共振成像用于测量SA和TH的全球和34个功能区域。使用逆方差加权作为主要估计值，而使用MR多效性残差和和离群值、MR Egger和加权中位数检测异质性和多效性。在整体水平上，蛋白尿降低TH（β = −0.07 mm，95% CI：−0.12 mm至−0.02 mm，P = 0.004）;在功能水平上，蛋白尿降低了未进行整体加权的盖部脑回TH（β = −0.11 mm，95% CI：−0.16 mm至−0.07 mm，P = 3.74×10−6）。未检测到多效性。肾损伤会影响皮质结构，这表明存在肾-脑轴。本研究得到了广东省科技计划项目的资助（批准号：2020 A151511119、2017 B 020227007），国家重点研发计划（批准号：2018 YFA 0902803），国家自然科学基金（批准号：81825016、81961128027、81772719、81772728），广东省重点领域研究发展计划（批准号：2018 B 010109006），广东省特别扶助计划（2017 TX 04 R246），广东省高等学校恶性肿瘤基因调控与靶向治疗重点实验室资助KLB 09001，及广东省科学技术厅赠款（2020 B1212060018）。
Alterations in the brain cortical structures of patients with chronic kidney disease (CKD) have been reported; however, the cause has not been determined yet. Herein, we used Mendelian randomization (MR) to reveal the causal effect of kidney damage on brain cortical structure. Genome-wide association studies summary data of estimated glomerular filtration rate (eGFR) in 480,698 participants from the CKDGen Consortium were used to identify genetically predicted eGFR. Data from 567,460 individuals from the CKDGen Consortium were used to assess genetically determined CKD; 302,687 participants from the UK Biobank were used to evaluate genetically predicted albuminuria. Further, data from 51,665 patients from the ENIGMA Consortium were used to assess the relationship between genetic predisposition and reduced eGFR, CKD, and progressive albuminuria with alterations in cortical thickness (TH) or surficial area (SA) of the brain. Magnetic resonance imaging was used to measure the SA and TH globally and in 34 functional regions. Inverse-variance weighted was used as the primary estimate whereas MR Pleiotropy RESidual Sum and Outlier, MR-Egger and weighted median were used to detect heterogeneity and pleiotropy. At the global level, albuminuria decreased TH (β = −0.07 mm, 95% CI: −0.12 mm to −0.02 mm, P = 0.004); at the functional level, albuminuria reduced TH of pars opercularis gyrus without global weighted (β = −0.11 mm, 95% CI: −0.16 mm to −0.07 mm, P = 3.74×10−6). No pleiotropy was detected. Kidney damage causally influences the cortex structure which suggests the existence of a kidney-brain axis. This study was supported by the Science and Technology Planning Project of Guangdong Province (Grant No. 2020A1515111119 and 2017B020227007), the National Key Research and Development Program of China (Grant No. 2018YFA0902803), the National Natural Science Foundation of China (Grant No. 81825016, 81961128027, 81772719, 81772728), the Key Areas Research and Development Program of Guangdong (Grant No. 2018B010109006), Guangdong Special Support Program (2017TX04R246), Grant KLB09001 from the Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, and Grants from the Guangdong Science and Technology Department (2020B1212060018).
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影响因子：
4
作者：
Chen X;Kong J;Diao X;Cai J;Zheng J;Xie W;Qin H;Huang J;Lin T
通讯作者：
Lin T
CKD儿童和年轻人的脑磁共振成像发现。
DOI：
10.1053/j.ajkd.2017.11.024
发表时间：
2018-09
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Hartung EA;Erus G;Jawad AF;Laney N;Doshi JJ;Hooper SR;Radcliffe J;Davatzikos C;Furth SL
通讯作者：
Furth SL
影响因子：
7.8
作者：
Inhof, Orsolya;Zsido, Andras N.;Darnai, Gergely
通讯作者：
Darnai, Gergely
影响因子：
--
作者：
Lin, Yu;Zhang, Kai;Yang, Xuejun
通讯作者：
Yang, Xuejun
DOI：
10.1016/s0140-6736(17)32152-9
发表时间：
2017-09-16
期刊：
Lancet (London, England)
影响因子：
--
作者：
GBD 2016 Causes of Death Collaborators
通讯作者：
GBD 2016 Causes of Death Collaborators