基于孟德尔随机化方法研究胰岛素样生长因子对神经退行性疾病的影响  

The effect of insulin-like growth factor on neurodegenerative diseases based on Mendelian randomization

作　　者：冯琳 李萌[1] 潘浩东 王丽华[1] 李千 FENG Lin;LI Meng;PAN Haodong;WANG Lihua;LI Qian(Department of Neurology,the Second Affiliated Hospital of Harbin Medical University,Harbin 150081,China;Department of Neurology,Beijing Children′s Hospital Heilongjiang Hospital;不详)

机构地区：[1]哈尔滨医科大学第二附属医院神经内科,哈尔滨150081 [2]北京儿童医院黑龙江医院神经内科,哈尔滨150010

出　　处：《中国临床保健杂志》2025年第1期72-77,共6页Chinese Journal of Clinical Healthcare

基　　金：黑龙江省自然科学基金项目(YQ2021H011)。

摘　　要：目的使用孟德尔随机化方法研究胰岛素样生长因子(IGF)与神经退行性疾病之间的因果关系。方法基于全基因组关联研究(GWAS)获取汇总统计数据,以基因决定的胰岛素样生长因子家族的血清水平为暴露因素,以神经退行性疾病的患病风险为结局,使用包括逆方差加权法(IVW)、MR-Egger法等5种孟德尔随机化(MR)分析方法,并对结果进行了包括Cochran′s Q检验、MR-Egger截距测试等多项敏感性分析,筛查结果是否存在异质性和水平多效性,以确保结果的稳健性。结果IVW分析显示,遗传预测的高水平胰岛素样生长因子结合蛋白(IGFBP)-5与多发性硬化患病风险增加之间存在显著关联(P=0.042,OR=1.121,95%CI:1.004~1.252),敏感性分析显示不存在水平多效性或异质性。此外,反向MR分析显示不存在反向因果关系。结论血清IGFBP-5水平升高是多发性硬化的危险因素。Objective To employ Mendelian randomization(MR)to unravel the associations between serum insulin-like growth factor(IGF)family member levels and neurodegenerative diseases.Methods Genetic instruments for IGF family members and diabetes were derived from summary-level genome-wide association study(GWAS)data,both with levels of IGF as exposure and risk of neurodegenerative diseases as an outcome.Five MR methods,including Inverse Variance Weighted(IVW)and MR-Egger approaches,were employed.Sensitivity analyses including Cochran′s Q test and MR-Egger intercept were conducted to ensure robustness.Results The IVW analysis revealed a significant association between genetically predicted higher levels of IGFBP-5 and an increased risk of multiple sclerosis(P=0.042,OR=1.121,95%CI:1.004-1.252).No evidence of horizontal pleiotropy or statistical heterogeneity was observed.Furthermore,reverse MR analysis did not indicate any causal effect of multiple sclerosis on IGFBP-5 levels.Conclusion Elevated serum IGFBP-5 level is a risk factor for multiple sclerosis.

关 键 词：神经退行性疾病 多发性硬化 胰岛素样生长因子结合蛋白5 孟德尔随机化分析 危险因素 

分 类 号：R73[医药卫生—肿瘤]