Relationship between educational attainment and non-alcoholic fatty liver disease: A two-sample Mendelian randomization study

BACKGROUND: Observational studies have identified an inverse association between education and non-alcoholic fatty liver disease (NAFLD). However, it is not possible to establish causality for this relationship. AIMS: To gain more insight into the causal nature of the relationship between education and NAFLD. METHODS: We performed two-sample Mendelian randomization (MR) analyses using summary-level, large-scale datasets to study the association of genetically predicted educational attainment (n = 1271 genetic instruments, obtained from 1,131,881 participants) with risk of NAFLD (i.e., liver fat [n = 32,858 participants] and electronic health record (EHR)-based NAFLD [n = 778,614 participants]). In sensitivity analyses, educational attainment was replaced by three education-related traits (i.e., genetically predicted cognition, math ability and highest math). RESULTS: Inverse-variance weighted method showed a statistically significant association between genetically predicted educational attainment and liver fat (beta: -0.251, 95%CI: -0.305; -0.198) and EHR-based NAFLD (OR: 0.609, 95%CI: 0.547; 0.677). MR-Egger regression did not show statistically significant intercepts. Similar findings were obtained when other MR tests were used or when educational attainment was replaced by education-related traits. CONCLUSIONS: This study suggests a causal, protective effect of higher education on NAFLD risk. Societal interventions targeted at people with low education are needed to alleviate the burden of NAFLD.