教育程度对慢性肝病的因果影响及其中介途径：孟德尔随机化研究。
Causal impacts of educational attainment on chronic liver diseases and the mediating pathways: Mendelian randomization study.
机构信息
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
出版信息
Liver Int. 2023 Nov;43(11):2379-2392. doi: 10.1111/liv.15669. Epub 2023 Jul 6.
BACKGROUND AND AIMS
Educational attainment is an essential socio-economic indicator with broad implications for lifestyle behaviour and metabolic health. We aimed to investigate the causal effect of education on chronic liver diseases and the potential mediating pathways.
METHODS
We applied univariable Mendelian randomization (MR) to assess the causal associations between educational attainment and non-alcoholic fatty liver disease (NAFLD) (cases/controls: 1578/307 576 in FinnGen; 1664/400 055 in UK Biobank), viral hepatitis (1772/307 382; 1215/403 316), hepatomegaly (199/222 728; 297/400 055), chronic hepatitis (699/301 014; 277/403 316), cirrhosis (1362/301 014; 114/400 055) and liver cancer (518/308 636; 344/393 372) using summary statistics of genome-wide association studies from the FinnGen Study and the UK Biobank, respectively. We used two-step MR to evaluate potential mediators and their mediation proportions in the association.
RESULTS
Meta-analysis of inverse variance weighted MR estimates from FinnGen and UK Biobank showed that genetically predicted 1-SD (4.2 years) higher education was causally associated with decreased risks of NAFLD (OR: 0.48; 95%CI: 0.37-0.62), viral hepatitis (0.54; 0.42-0.69) and chronic hepatitis (0.50; 0.32-0.79), but not hepatomegaly, cirrhosis and liver cancer. Nine, two and three out of 34 modifiable factors were identified as causal mediators in the associations of education with NAFLD, viral hepatitis and chronic hepatitis, respectively, including six adiposity traits (mediation proportion: 16.5%-32.0%), major depression (16.9%), two glucose metabolism-related traits (2.2%-15.8%) and two lipids (9.9%-12.1%).
CONCLUSIONS
Our findings supported the causal protective effects of education on chronic liver diseases and outlined mediating pathways to inform prevention and intervention strategies to reduce the burden of liver diseases, especially for individuals with lower education.
背景和目的
教育程度是一个重要的社会经济指标，对生活方式行为和代谢健康有广泛影响。我们旨在研究教育程度对慢性肝病的因果影响及其潜在的中介途径。
方法
我们应用单变量孟德尔随机化（MR）来评估教育程度与非酒精性脂肪性肝病（NAFLD）（病例/对照：FinnGen 中为 1578/307576；UK Biobank 中为 1664/400055）、病毒性肝炎（1772/307382；1215/403316）、肝肿大（199/222728；297/400055）、慢性肝炎（699/301014；277/403316）、肝硬化（1362/301014；114/400055）和肝癌（518/308636；344/393372）之间的因果关联，使用 FinnGen 研究和 UK Biobank 中的全基因组关联研究的汇总统计数据。我们使用两步 MR 来评估关联中的潜在中介因素及其中介比例。
结果
FinnGen 和 UK Biobank 的逆方差加权 MR 估计值的荟萃分析表明，遗传预测的 1-SD（4.2 年）更高的教育程度与降低 NAFLD（OR：0.48；95%CI：0.37-0.62）、病毒性肝炎（0.54；0.42-0.69）和慢性肝炎（0.50；0.32-0.79）的风险相关，但与肝肿大、肝硬化和肝癌无关。在教育程度与 NAFLD、病毒性肝炎和慢性肝炎的关联中，确定了 34 个可改变因素中的 9 个、2 个和 3 个为因果中介因素，包括 6 个肥胖特征（中介比例：16.5%-32.0%）、重度抑郁症（16.9%）、2 个与葡萄糖代谢相关的特征（2.2%-15.8%）和 2 个脂质（9.9%-12.1%）。
结论
我们的研究结果支持了教育程度对慢性肝病的保护作用，并概述了中介途径，为预防和干预策略提供了信息，以减轻肝病负担，特别是针对受教育程度较低的人群。
Zotero 插件