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利用基因分析研究教育程度与2型糖尿病之间的因果关系:来自EPIC-InterAct研究的孟德尔随机化结果

Examining causal relationships between educational attainment and type 2 diabetes using genetic analysis: findings from the EPIC-InterAct study through Mendelian randomisation.

作者信息

Macciotta Alessandra, Sacerdote Carlotta, Giachino Claudia, Di Girolamo Chiara, Franco Matteo, van der Schouw Yvonne T, Zamora-Ros Raul, Weiderpass Elisabete, Domenighetti Cloé, Elbaz Alexis, Truong Thérèse, Agnoli Claudia, Bendinelli Benedetta, Panico Salvatore, Vineis Paolo, Christakoudi Sofia, Schulze Matthias B, Katzke Verena, Bajracharya Rashmita, Dahm Christina C, Dalton Susanne Oksbjerg, Colorado-Yohar Sandra M, Moreno-Iribas Conchi, Etxezarreta Pilar Amiano, Sanchez María José, Forouhi Nita G, Wareham Nicholas, Ricceri Fulvio

机构信息

Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.

Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.

出版信息

J Epidemiol Community Health. 2025 Apr 10;79(5):373-379. doi: 10.1136/jech-2024-222734.

Abstract

INTRODUCTION

Observational studies have shown that more educated people are at lower risk of developing type 2 diabetes (T2D). However, robust study designs are needed to investigate the likelihood that such a relationship is causal. This study used genetic instruments for education to estimate the effect of education on T2D using the Mendelian randomisation (MR) approach.

METHODS

Analyses have been conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study (more than 20 000 individuals), a case-cohort study of T2D nested in the EPIC cohort. Education was measured as Years of Education and Relative Index of Inequality. Prentice-weighted Cox models were performed to estimate the association between education and T2D. One-sample MR analyses investigated whether genetic predisposition towards longer education was associated with risk of T2D and investigated potential mediators of the association.

RESULTS

MR estimates indicated a risk reduction of about 15% for each year of longer education on the risk of developing T2D, confirming the protective role estimated by observational models (HR 0.96, 95% CI 0.95 to 0.96). MR analyses on putative mediators showed a significant role of education on body mass index, alcohol consumption, adherence to the Mediterranean diet and smoking habits.

CONCLUSION

The results supported the hypothesis that higher education is a protective factor for the risk of developing T2D. Based on its position in the causal chain, education may be antecedent of other known risk factors for T2D including unhealthy behaviours. These findings reinforce evidence obtained through observational study designs and bridge the gap between correlation and causation.

摘要

引言

观察性研究表明,受教育程度较高的人患2型糖尿病(T2D)的风险较低。然而,需要强有力的研究设计来调查这种关系为因果关系的可能性。本研究使用教育的遗传工具,采用孟德尔随机化(MR)方法来估计教育对T2D的影响。

方法

在欧洲癌症与营养前瞻性调查(EPIC)-InterAct研究(超过20000人)中进行了分析,这是一项嵌套在EPIC队列中的T2D病例队列研究。教育程度以受教育年限和不平等相对指数来衡量。采用Prentice加权Cox模型来估计教育与T2D之间的关联。单样本MR分析调查了接受更长时间教育的遗传易感性是否与T2D风险相关,并调查了该关联的潜在中介因素。

结果

MR估计表明,每多接受一年教育,患T2D的风险降低约15%,证实了观察模型所估计的保护作用(风险比0.96,95%置信区间0.95至0.96)。对假定中介因素的MR分析表明,教育对体重指数、饮酒量、坚持地中海饮食和吸烟习惯有显著作用。

结论

结果支持了高等教育是T2D发病风险保护因素的假设。基于其在因果链中的位置,教育可能是T2D其他已知风险因素(包括不健康行为)的前因。这些发现强化了通过观察性研究设计获得的证据,并弥合了相关性与因果关系之间的差距。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6394/12015027/1bc518b496ae/jech-79-5-g001.jpg

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