Mendelian randomization analyses support causal relationships between brain imaging-derived phenotypes and risk of psychiatric disorders.

Observational studies have reported the correlations between brain imaging-derived phenotypes (IDPs) and psychiatric disorders; however, whether the relationships are causal is uncertain. We conducted bidirectional two-sample Mendelian randomization (MR) analyses to explore the causalities between 587 reliable IDPs (N = 33,224 individuals) and 10 psychiatric disorders (N = 9,725 to 161,405). We identified nine IDPs for which there was evidence of a causal influence on risk of schizophrenia, anorexia nervosa and bipolar disorder. For example, 1 s.d. increase in the orientation dispersion index of the forceps major was associated with 32% lower odds of schizophrenia risk. Reverse MR indicated that only genetically predicted schizophrenia was positively associated with two IDPs, the cortical surface area and the volume of the right pars orbitalis. We established the BrainMR database ( http://www.bigc.online/BrainMR/ ) to share our results. Our findings provide potential strategies for the prediction and intervention for psychiatric disorder risk at the brain-imaging level.