IntroductionSchizophrenia is a severe and chronic psychiatric disorder with hereditary risk up to 80% as previous studies indicated. Several researches have demonstrated a significant association between schizophrenia and microduplications that overlap the vasoactive intestinal peptide receptor 2 gene (VIPR2).MethodsTo further investigate potential causalVIPR2gene variants, all exons and un-translated portions of theVIPR2gene were sequenced using amplicon targeted resequencing in 1804 Chinese Han patients with schizophrenia and 996 healthy counterparts in the present study.ResultsNineteen rare non-synonymous mutations and 1 frameshift deletion was identified for schizophrenia, among which 5 variants have never been reported so far. Frequencies of rare non-synonymous mutations were significantly different between the two groups. Specifically, the non-synonymous mutation rs78564798 (Pallele= 0.006) as well as two rare variations in theVIPR2gene’s introns (rs372544903,Pallele= 0.026 and a novel mutation, chr7:159034078, GRCh38,Pallele= 0.048) were significantly associated with schizophrenia.DiscussionOur findings add new evidence that the functional and probable causative variants ofVIPR2gene may play an important role in susceptibility to schizophrenia. Further studies on validations ofVIPR2’s function in the etiology of schizophrenia are warranted.