摘要
目的探究虚弱指数(frailty Index;FI)、水肿和抑郁在慢性肾脏病(chronic kidney disease,CKD)患者中对四肢瘦体质量(appendicular lean mass,ALM)的基因因果关系,为CKD相关肌肉减少症的预防提供依据。方法基于公开的全基因组关联研究(genome-wide association studies,GWAS)数据库,提取与FI、水肿、抑郁、CKD及ALM相关的全基因组关联(genome-wide association study,GWAS)摘要数据。首先,采用两步法孟德尔随机化(two-step Mendelian randomization,Two-step MR)确定CKD与ALM之间可能的中介因子。随后,通过多变量孟德尔随机化(multivariable Mendelian randomization,MVMR)分析,筛选出与ALM独立相关的因果变量。最后,构建中介MR模型,将CKD设为暴露因素,ALM设为结局变量,以显著的独立因果变量作为中介,探讨潜在的中介路径。结果经Two-step MR、MVMR及中介MR分析,结果显示FI为CKD与ALM之间的潜在独立中介因子(OR=0.458,95%CI:0.411~0.511,P=0.021)。进一步分析表明,CKD通过FI对ALM存在显著的中介因果作用(β_(中介效应量)=-0.24,OR=0.787,95%CI:0.67~0.978,P=0.019)。结论CKD对ALM的影响主要经虚弱状态间接实现,虚弱是CKD相关肌肉减少症的重要中介因素,为临床干预提供遗传机制依据。
Objective To investigate frailty index(FI),edema,and depression in the genetic causal relationship between chronic kidney disease(CKD)and appendicular lean mass(ALM),in order to provide references for the prevention of CKD-related sarcopenia.Methods Summary data for FI,edema,depression,CKD,and ALM were obtained from publicly available genome-wide association study(GWAS)databases.A two-step Mendelian randomization(MR)approach was first applied to evaluate potential mediators between CKD and ALM.Subsequently,multivariable Mendelian randomization(MVMR)analysis was conducted to identify causal factors independently associated with ALM.Finally,a mediation MR model was constructed,with CKD as the exposure,ALM as the outcome,and the identified independent causal factors as mediators to explore potential mediation pathways.Results Two-step MR,MVMR,and mediation MR analyses revealed that FI is a potential independent mediator between CKD and ALM(OR=0.458,95%CI:0.411~0.511,P=0.021).Further mediation analysis indicated a significant indirect causal effect of CKD on ALM through FI(β_(mediation effect)=-0.24,OR=0.787,95%CI:0.67~0.978,P=0.019).Conclusion The effect of CKD on ALM is primarily mediated indirectly through frailty.Frailty serves as a key mediator of CKD-related sarcopenia,providing a genetic basis for clinical intervention of sarcopenia.
作者
马晨红
张玉彩
姚书格
李翠霞
张丽君
郭云岭
MA Chen-hong;ZHANG Yu-cai;YAO Shu-ge;LI Cui-xia;ZHANG Lijun;GUO Yun-ling(Sterile Supply Center,The Second Affiliated Hospital of Xingtai Medical College,Xingtai 054002,China;Department of Nephrology,The Second Affiliated Hospital of Xingtai Medical College,Xingtai 054002,China;Department of Radiology,The Second Affiliated Hospital of Xingtai Medical College,Xingtai 054002,China;Department of Traditional Chinese Medicine,The Second Affiliated Hospital of Xingtai Medical College,Xingtai 054002,China)
出处
《中国血液净化》
2026年第4期310-315,共6页
Chinese Journal of Blood Purification
基金
邢台市重点研发计划(2021ZC181)。
关键词
慢性肾脏病
虚弱
水肿
抑郁
四肢瘦体质量
两步法孟德尔随机化
多变量孟德尔随机化
中介孟德尔随机化
Chronic kidney disease
Frailty
Edema
Depression
Appendicular lean mass
Two-step Mendelian randomization
Multivariable Mendelian randomization
Mediation Mendelian randomization
