Suggestive associations have been reported between trace amines and heat shock proteins, and a disrupted pathophysiology that enhances the risk of psychosis and that modifies responses to antipsychotic treatments. Our group previously reported genetic studies on TAAR6 and HSP-70 separately in patients with schizophrenia. In the current study, we investigated possible epistasis between the same set of variations in a sample of 281 patients diagnosed with schizophrenia and 288 healthy controls. We applied the generalized multifactor dimensionality reduction (MDR) method and controlled covariates significantly associated with both diagnosis and treatment efficacy. To the best of our knowledge, epistasis between the present set of variations in schizophrenia has not been tested before. We found significant associations with both the risk of disease and response to treatment. However, the insufficiently balanced accuracy of the applied tests suggests that, despite significantly different genetic variations between cases and controls, these factors have a poor predictive value. Explanations for these findings and possible future directions are also discussed.