Causal impacts of educational attainment on chronic liver diseases and the mediating pathways: Mendelian randomization study

Author:

Wang Yiying12,Kong Lijie12,Ye Chaojie12,Dou Chun12,Zheng Jie12,Xu Min12ORCID,Xu Yu12,Li Mian12ORCID,Zhao Zhiyun12,Lu Jieli12ORCID,Chen Yuhong12ORCID,Wang Weiqing12,Ning Guang12,Bi Yufang12,Wang Tiange12ORCID

Affiliation:

1. Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China

2. 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

Abstract

AbstractBackground and AimsEducational 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.MethodsWe 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.ResultsMeta‐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%).ConclusionsOur 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.

Publisher

Wiley

Subject

Hepatology

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