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循环胰岛素样生长因子-1与帕金森病之间的因果关系:一项两样本孟德尔随机化研究

Causal relationship between circulating insulin-like growth factor-1 and Parkinson's disease: a two-sample Mendelian randomization study.

作者信息

Xu Jiahao, Fan Peidong, Yang Jiacheng, Yin Mingjuan, Wu Jun, Chen Chao, Ni Jindong

机构信息

Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Medical University, Dongguan, China.

Department of Neurology, Second Hospital Affiliated of Xinjiang Medical University, Xinjiang, China.

出版信息

Front Aging Neurosci. 2024 Apr 17;16:1333289. doi: 10.3389/fnagi.2024.1333289. eCollection 2024.

Abstract

BACKGROUND

Linear associations between circulating insulin-like growth factor-1 (IGF-1) levels and Parkinson's disease (PD) have been evidenced in observational studies. Yet, the causal relationship between IGF-1 levels and PD remains obscure. We conducted Mendelian randomization to examine the correlation between genetically predicted IGF-1 levels and PD.

METHODS

By reviewing genome-wide association studies (GWAS) that are publicly accessible, we uncovered SNPs linked to both serum concentrations of IGF-1 and PD. A two-sample Mendelian randomization (MR) analysis was carried out to evaluate the individual effect of IGF-1 on PD.

RESULTS

In a primary causal effects model in MR analysis, employing the inverse-variance weighted (IVW) method, IGF-1 levels exhibited a notable association with the risk of PD (OR, 1.020, 95% CI, 1.003-1.038,  = 0.0215). Multiple evaluations revealed that horizontal pleiotropy was improbable to distort the main results (MR-Egger: P PD intercept =0.719), and no bias was detected by leave-one-out analysis.

CONCLUSION

This study unearthed evidence indicating that heightened IGF-1 levels might be causally correlated with an increased risk of PD.

摘要

背景

观察性研究已证实循环胰岛素样生长因子-1(IGF-1)水平与帕金森病(PD)之间存在线性关联。然而,IGF-1水平与PD之间的因果关系仍不明确。我们进行了孟德尔随机化研究,以检验基因预测的IGF-1水平与PD之间的相关性。

方法

通过查阅公开可用的全基因组关联研究(GWAS),我们发现了与IGF-1血清浓度和PD均相关的单核苷酸多态性(SNP)。进行了两样本孟德尔随机化(MR)分析,以评估IGF-1对PD的个体效应。

结果

在MR分析的主要因果效应模型中,采用逆方差加权(IVW)方法,IGF-1水平与PD风险显著相关(比值比,1.020;95%置信区间,1.003 - 1.038;P = 0.0215)。多项评估表明,水平多效性不太可能扭曲主要结果(MR-Egger:P截距 = 0.719),留一法分析未检测到偏差。

结论

本研究发现证据表明,IGF-1水平升高可能与PD风险增加存在因果关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1fe/11064709/d6c901141cf6/fnagi-16-1333289-g001.jpg

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