"Genetically predicted adiponectin causally reduces the risk of chronic kidney disease, a bilateral and multivariable mendelian randomization study"

作者全名："Wu, Ruicheng; Luo, Peiyi; Luo, Min; Li, Xiaoyu; Zhong, Xin; He, Qiang; Zhang, Jie; Zhang, Yangchang; Xiong, Yang; Han, Ping"

作者地址："[Wu, Ruicheng; Luo, Min; Zhong, Xin; Zhang, Jie; Xiong, Yang; Han, Ping] Sichuan Univ, West China Hosp, Dept Urol, Chengdu, Peoples R China; [Luo, Peiyi] Sichuan Univ, West China Hosp, Dept Nephrol, Chengdu, Peoples R China; [Luo, Peiyi] Sichuan Univ, West China Hosp, Kidney Res Inst, Chengdu, Peoples R China; [Li, Xiaoyu] Chongqing Med Univ, Basic Med Expt Teaching Ctr, Lab Innovat, Chongqing, Peoples R China; [He, Qiang] Sichuan Univ, West China Hosp, Dept Neurosurg, Chengdu, Peoples R China; [Zhang, Yangchang] Chongqing Med Univ, Sch Publ Hlth & Management, Dept Epidemiol & Hlth Stat, Chongqing, Peoples R China"

通信作者："Han, P (通讯作者)，Sichuan Univ, West China Hosp, Dept Urol, Chengdu, Peoples R China."

来源：FRONTIERS IN GENETICS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000891265400001

JCR分区：Q2

影响因子：3.7

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：adiponectin; chronic kidney disease; estimated glomerular filtration rate; causal estimates; mendelian randomization

摘要："Background: It is not clarified whether the elevation of adiponectin is the results of kidney damage, or the cause of kidney function injury. To explore the causal association of adiponectin on estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD), this study was performed. Materials and methods: The genetic association of adiponectin were retrieved from one genome-wide association studies with 39,883 participants. The summary-level statistics regarding the eGFR (133,413 participants) and CKD (12,385 CKD cases and 104,780 controls) were retrieved from the CKDGen consortium in the European ancestry. Single-variable Mendelian randomization (MR), bilateral and multivariable MR analyses were used to verify the causal association between adiponectin, eGFR, and CKD. Results: Genetically predicted adiponectin reduces the risk of CKD (OR = 0.71, 95% CI = 0.57-0.89, p = 0.002) and increases the eGFR (beta = 0.014, 95% CI = 0.001-0.026, p = 0.034) by the inverse variance weighting (IVW) estimator. These findings remain consistent in the sensitivity analyses. No heterogeneity and pleiotropy were detected in this study (P for MR-Egger 0.617, P for global test > 0.05, and P for Cochran's Q statistics = 0.617). The bilateral MR identified no causal association of CKD on adiponectin (OR = 1.01, 95% CI = 0.96-1.07, p = 0.658), nor did it support the association of eGFR on adiponectin (OR = 0.86, 95% CI = 0.68-1.09, p = 0.207) by the IVW estimator. All the sensitivity analyses reported similar findings (p > 0.05). Additionally, after adjusting for cigarette consumption, alcohol consumption, body mass index, low density lipoprotein, and total cholesterol, the ORs for CKD are 0.70 (95% CI = 0.55-0.90, p = 0.005), 0.75 (95% CI = 0.58-0.97, p = 0.027), 0.82 (95% CI = 0.68-0.99, p = 0.039), 0.74 (95% CI = 0.59-0.93, p = 0.011), and 0.79 (95% CI = 0.61-0.95, p = 0.018), respectively. Conclusion: Using genetic data, this study provides novel causal evidence that adiponectin can protect the kidney function and further reduce the risk of CKD."

基金机构："Pillar Program from Department of Science and Technology of Sichuan Province [2018SZ0219]; 1.3.5 project f or disciplines of excellence, West China Hospital, Sichuan University [ZY2016104]"

基金资助正文："The study was supported by the Pillar Program from Department of Science and Technology of Sichuan Province (2018SZ0219) and the 1.3.5 project f or disciplines of excellence, West China Hospital, Sichuan University (ZY2016104)."