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

Abstract

BackgroundObservational 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. AimsTo gain more insight into the causal nature of the relationship between education and NAFLD. MethodsWe 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). ResultsInverse-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. ConclusionsThis 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.