Synergistic SNP-SNP interaction of NRG1 and ERBB4 increases the risk of schizophrenia

In last two decades, quite of few evidences were found about the genetic risk factor for schizophrenia. But until now, it's poorly understood that the pathogenesis of schizophrenia and contribution of those genetic factors in it. Inconsistent data reported for several candidate gene polymorphisms contributing on schizophrenia development, previously. The case-control study was conducted with 102 schizophrenia patients and 150 control subjects. HTR2A (rs6311), TPH2 (rs1386494), NRG1 (rs3924999 and rs2954041), DISC1 (rs821616 and rs6675281) and ERBB4 (rs7424835 and rs4673628) gene polymorphisms were detected by allele specific PCR and RFLP. Genetic analysis were performed by SNPAlyze 9.0 and STATA 13.0 software. Also, multidimensional regression analysis was used to determine the SNP-SNP interaction. T allele of rs821616 DISC1 and G allele of rs4673628 ERBB4, were associated with increased risk of schizophrenia. Significant difference was observed for heterozygous G/A genotype of rs6311 (G/A vs G/G + A/A, OR = 2.11; 95 % CI, 1.25-3.54, p = 0.005). By SNP-SNP interaction, the cumulative effect of NRG1 (rs3924999) and ERBB4 (rs4673628) combination, had increasing the risk of schizophrenia by 9.44-fold. This data require independent replication for rs821616, rs4673628 and rs6311 polymorphisms and schizophrenia risk. But particularity, our result suggests the interaction, rs3924999-rs4673628 of NRG1 and ERBB4 genes surprisingly increases the risk of schizophrenia.