identified NKCC1 as a potential susceptibility gene for schizophrenia (Potkin et al., 2009). Furthermore, NKCC1 expression in the dorsolateral prefrontal cortex of some schizophrenia patients was over seven times higher (Dean et al., 2007) and the ratio of NKCC1/KCC2 is increased in the hippocampus of patients with schizophrenia and related to genetic variation in GAD1 (Hyde et al., 2011). Our hypothesis-driven genetic association study of schizophrenia showed genetic epistasis between DISC1 and NKCC1, which, though relatively weak on a statistical level in individual samples, was replicated in two larger datasets with the same SNPs and combinations of genotypes. Importantly, the epistatic interaction remained significant in the combined analysis of three clinical case control datasets from three different countries. These typed SNPs tag common haplotypes that may contain functional variants and are proxies for untyped functional alleles. Indeed, these two specific SNPs appear to mark functional domains within the gene that impact gene function and show association with expression of specific exons within their respective genes in a brain mRNA expression dataset. In the context of the molecular data and given the consistency of the same genotypes showing predicted interactions across diverse clinical datasets, the convergent results support a role for
