In the largest genetic study of schizophrenia thus far, we explore the genomic architecture of and the evolutionary pressures on common variants associated with the disorder. Our study provides the first evidence linking common variation in LoF-intolerant genes to risk of developing schizophrenia and demonstrates that these genes account for a substantial proportion (30%) of the SNP-based heritability for schizophrenia. Systems genomics analysis highlights six gene sets that are independently associated with schizophrenia and point to molecular, physiological and behavioral pathways involved in schizophrenia pathogenesis.
