Genetic risk and transdiagnostic traits in anorexia nervosa, obsessive-compulsive disorder, and schizophrenia

Background. Shared genetic risk has been shown across psychiatric disorders. In particular, anorexia nervosa (AN), obsessive-compulsive disorder (OCD), and schizophrenia (SCZ) show shared genetic risk that matches clinical evidence of shared illness and cognitive phenotypes. Given this evidence, we leveraged a large US-based population-based study to determine genetic associations of disorder-specific and shared psychiatric, cognitive, and brain markers and explore whether the latter might be state versus trait markers in eating disorders. Methods. We used data from the population-based Philadelphia Neurodevelopmental Cohort (N = 4,729) and conducted sex-stratified analyses to test for associations between genetic risk for three disorders (AN, OCD, and SCZ) and mental health phenotypes, neurocognitive traits, and cortical features in a non-clinical population. Exploratory analyses on cortical features were run on a subset with neuroimaging data (N = 626). Results. Genetic risk for AN was significantly associated with body image distortion (p _FDR = 0.02), and body image distortion was significantly related to a reduction in grey matter volume (p _FDR = 0.05). Conclusion. Genetic risk for AN associates with AN trait in a non-clinical sample of youth, particularly in females. Whilst genetic risk was not associated with cognitive or cortical markers, the AN phenotype was associated with cortical markers.