Among the 40 genes, 8 genes (LRP1, ABCA2, CEP170, HTRA2, DICER1, MACF1, ADAMTS15 and SEMA3F) occurred in the top 1000 constrained gene list (p = 9.8 × 10−4, hypergeometric test based on 18,988 CCDS protein coding genes) (Table S3), suggesting it is unlikely that these genes harbor de novo mutations only by chance in our schizophrenic patients, and the occurrence of de novo mutations may be related to schizophrenia. This evidence concerns the gene HTRA2 and schizophrenia.