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

Yiying Wang; Lijie Kong; Chaojie Ye; Chun Dou; Jie Zheng; Min Xu; Yu Xu; Mian Li; Zhiyun Zhao; Jieli Lu; Yuhong Chen; Weiqing Wang; Guang Ning; Yufang Bi; Tiange Wang

doi:10.1111/liv.15669

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

Liver Int. 2023 Nov;43(11):2379-2392. doi: 10.1111/liv.15669. Epub 2023 Jul 6.

Authors

Yiying Wang^{1

2}, Lijie Kong^{1

2}, Chaojie Ye^{1

2}, Chun Dou^{1

2}, Jie Zheng^{1

2}, Min Xu^{1

2}, Yu Xu^{1

2}, Mian Li^{1

2}, Zhiyun Zhao^{1

2}, Jieli Lu^{1

2}, Yuhong Chen^{1

2}, Weiqing Wang^{1

2}, Guang Ning^{1

2}, Yufang Bi^{1

2}, Tiange Wang^{1

2}

Affiliations

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.

PMID: 37409353
DOI: 10.1111/liv.15669

Abstract

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.

Keywords: NAFLD; chronic hepatitis; mediating pathway; modifiable risk factors; viral hepatitis.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Educational Status
Genome-Wide Association Study
Hepatitis, Chronic
Hepatitis, Viral, Human*
Hepatomegaly
Humans
Liver Cirrhosis / epidemiology
Liver Cirrhosis / genetics
Liver Neoplasms* / epidemiology
Liver Neoplasms* / genetics
Mendelian Randomization Analysis
Non-alcoholic Fatty Liver Disease* / epidemiology
Non-alcoholic Fatty Liver Disease* / genetics
Polymorphism, Single Nucleotide