握力减低与NAFLD的因果关系:一项孟德尔随机化研究

Causal relationship between low hand grip strength and NAFLD:a Mendelian randomization study

目的使用孟德尔随机化(MR)分析方法,探究握力减低与非酒精性脂肪性肝病(NAFLD)的因果关系。方法以握力减低作为暴露因素,以NAFLD作为结局因素,在全基因组关联研究(GWAS)数据库中筛选出合适的工具变量(IVs)进行MR分析。选择逆方差加权法(IVW)、加权中位数法(WME)、ME-Egger法作为主要分析方法。使用Cochran Q检验、MR-Egger截距法、留一法进行异质性及敏感性分析。结果IVW法和WME法均显示握力减低是NAFLD的危险因素(IVW法:OR=1.46,95%CI:1.10~1.94,P<0.01;WME法:OR=1.48,95%CI:1.06~2.06,P<0.05)。MR-Egger回归并未说明握力减低是NAFLD的危险因素,但其OR值与IVW及WME的OR值方向一致(OR=1.38,95%CI:0.66~2.85,P>0.05)。异质性分析IVW检验和MR-Egger检验均表明不存在显著异质性。MR-Egger回归分析显示该因果关系之间不存在水平多效性。MR-PRESSO分析并未发现离群值。留一法分析并未发现存在对因果关系有较大影响的单一SNP。结论握力降低与NAFLD患病风险增加相关。该研究结果有助于进一步认识肌少症与NAFLD之间的关系,并为NAFLD的预防和治疗提供新的诊疗方向。

Objective Mendelian randomization was used to explore the causal relationship between low hand grip strength and NAFLD.Methods Using low hand grip strength as the exposure factor and NAFLD as the outcome factor,appropriate IVs were screened in the GWAS database for MR.The main analysis methods are IVW,WME,and ME Egger method.Heterogeneity analysis and sensitivity analysis were conducted using Cochran Q test,MR Egger,and leave one out method.Results Both IVW and WME indicate that low hand grip strength is a risk factor for NAFLD(IVW:OR=1.46,95%CI:1.10~1.94,P<0.01;WME:OR=1.48,95%CI:1.06~2.06,P<0.05).The MR Egger regression did not indicate that low hand grip strength is a risk factor for NAFLD,but its OR value is consistent with the direction of OR values for IVW and WME(OR=1.38,95%CI:0.66~2.85,P>0.05).Heterogeneity analysis showed no significant heterogeneity.MR Egger shows that there is no horizontal pleiotropy between the causal relationship.MR-PRESSO did not detect outliers.The leave one out method did not find the existence of a single SNP that has a significant impact on causal relationship.Conclusion Low hand grip strength is associated with an increased risk of NAFLD.This research result helps to further understand the relationship between sarcopenia and NAFLD,and provides new diagnostic and therapeutic directions for the prevention and treatment of NAFLD.