Educational attainment and psychiatric diagnoses: a national registry data and two-sample Mendelian randomization study

We investigate the causal relationship between educational attainment (EA) and mental health conditions using two research designs. Here we first compare the relationship between EA and 18 psychiatric diagnoses within-sibship in Dutch national registry data (N = 1.7 million), thereby controlling for unmeasured familial factors. Second, we apply two-sample Mendelian randomization, which uses genetic variants related to EA or psychiatric diagnosis as instrumental variables, to test whether there is a causal relation in either direction. Our results suggest that lower levels of EA causally increase the risk of major depressive disorder, attention-deficit/hyperactivity disorder, alcohol dependence, generalized anxiety disorder and post-traumatic stress disorder diagnoses. We also find evidence of a causal effect of attention-deficit/hyperactivity disorder on EA. For schizophrenia, anorexia nervosa, obsessive–compulsive disorder and bipolar disorder, the results were inconsistent across the different approaches, highlighting the importance of using multiple research designs to understand complex relationships, such as between EA and mental health conditions. Analyzing national registry data, the authors use within-sibling design and two-sample Mendelian randomization to identify bidirectional causal relationships between educational attainment (EA) and mental health conditions, demonstrating that lower levels of EA were differentially associated with some disorders, such as major depressive disorder, but that attention-deficit/hyperactivity disorder causally affected EA.