Kidney damage causally affects the brain cortical structure: A Mendelian randomization study

作者：Xiong Chen, Jianqiu Kong, Jiexin Pan, Kai Huang, Wenhao Zhou, Xiayao Diao, Jiahao Cai, Junjiong Zheng, Xuefan Yang, Weibin Xie, Hao Yu, Jiande Li, Lu Pei, Wen Dong, Haide Qin, Jian Huang, Tianxin Lin · 发表于：EBioMedicine · 年份：2021 · DOI：10.1016/j.ebiom.2021.103592 · 被引用次数：288 · 研究领域：Genetic Associations and Epidemiology、Chronic Kidney Disease and Diabetes、Functional Brain Connectivity Studies

BACKGROUND: 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. METHODS: 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. FINDINGS: ). No pleiotropy was detected. INTERPRETATION: Kidney damage causally influences the cortex structure which suggests the existence of a kidney-brain axis. FUNDING: This study was supported by the Science and Technology Planning Project of Guangdon...