<p>Observational epidemiology suggests a link between the dermatological disorder acne vulgaris and several psychiatric disorders. However, the biological mechanisms that underlie the relationship between acne and mental health are poorly characterised. Here, we employed a genetic approach using large-scale genome-wide association studies of acne and ten psychiatric disorders to both estimate causal effects and uncover potential shared genetic risk factors. Multiple psychiatric disorders displayed evidence of small-to-moderate genetic correlations with acne. However, only genetic liability to schizophrenia displayed some evidence of a causal effect on the risk of acne, though horizontal pleiotropy cannot be fully excluded. Using a Gaussian mixture-model based approach, we then identified a cluster of schizophrenia-associated variants with distinct effects on acne liability, refining the molecular mechanisms that may link schizophrenia and acne. Shared genetic risk architecture between schizophrenia and acne was also investigated using Bayesian approaches. This revealed a subset of genetic loci associated with both acne and schizophrenia via shared or different causal variants, implicating biological processes including glutamatergic signalling. Finally, we found that genetic risk for schizophrenia was also associated with increased acne severity using a population-based cohort. In summary, we revealed genetic support for a biological relationship between acne and schizophrenia that may at least partially drive the elevated rates of acne amongst people living with schizophrenia.</p>