Genetic estimation of causalities between educational attainment with common digestive tract diseases and the mediating pathways

The association between education, intelligence, and cognition with digestive tract diseases has been established. However, the specific contribution of each factor in the pathogenesis of these diseases are still uncertain. This study employed multivariable Mendelian randomization (MR) to assess the independent effects of education, intelligence, and cognition on gastrointestinal conditions in the FinnGen and UK Biobank European-ancestry populations. A two-step MR approach was employed to assess the mediating effects of the association. Meta-analysis of MR estimates from FinnGen and UK Biobank showed that 1- SD (4.2 years) higher education was causally associated with lower risks of gastroesophageal reflux (OR: 0.58; 95% CI: 0.50, 0.66), peptic ulcer (OR: 0.57; 95% CI: 0.47, 0.69), irritable bowel syndrome (OR: 0.70; 95% CI: 0.56, 0.87), diverticular disease (OR: 0.69; 95% CI: 0.61, 0.78), cholelithiasis (OR: 0.68; 95% CI: 0.59, 0.79) and acute pancreatitis (OR: 0.54; 95% CI: 0.41, 0.72), independently of intelligence and cognition. These causal associations were mediating by body mass index (3.7-22.3%), waist-to-hip ratio (8.3-11.9%), body fat percentage (4.1-39.8%), fasting insulin (1.4-5.5%) and major depression (6.0-12.4%). Our findings demonstrate a causal and independent association between education and six common digestive tract diseases. Additionally, our study highlights five mediators as crucial targets for preventing digestive tract diseases associated with lower education levels.