The role of histone modifications in the pathogenesis of schizophrenia has been proposed previously. H3F3B is a member of the histone 3. NSD2 is a histone methyltransferase that mediates dimethylation of Histone 3 lysine 36 (H3K36me2). The aim of the current study was to explore the associations between SNPs within H3F3B gene (rs60700976, rs3214028) and NSD2 gene (rs13148597, rs75820801) and the susceptibility to schizophrenia in a Chinese population. A total of 810 patients and 490 healthy controls were recruited and genetic association analyses were performed. The H3F3B gene polymorphisms rs3214028 and rs60700976 were significantly associated with schizophrenia. Rs60700976 was also associated with psychotic symptoms in schizophrenia patients. Furthermore, we found the interaction between NSD2 gene and H3F3B gene was related to the susceptibility to schizophrenia. The corresponding best three-locus model was H3F3B (rs60700976) - NSD2 (rs75820801, rs13148597), and the high-risk genotype combination was rs13148597(CC)- rs60700976(GG)-rs75820801(TT) (OR = 1.388[1.091-1.766], P = .007). The low-risk genotype combination was rs13148597(CC)-rs60700976(GG)-rs75820801(CT) (OR = 0.57 [0.330-0.985], P = .042). Our findings provided the preliminary evidence that the histone modification related H3F3B and NSD2 genes may confer the susceptibility to schizophrenia in a Chinese population.
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