TY - JOUR
T1 - Epistasis between a set of variations located in the TAAR6 and HSP-70 genes toward schizophrenia and response to antipsychotic treatment
AU - Pae, Chi-Un
AU - Drago, Antonio
AU - Patkar, Ashwin A
AU - Jun, Tae-Youn
AU - Serretti, Alessandro
PY - 2009/11
Y1 - 2009/11
N2 - 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.
AB - 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.
KW - Antipsychotic Agents/therapeutic use
KW - Cell Cycle Proteins/genetics
KW - Epistasis, Genetic
KW - Gene Frequency
KW - Genetic Predisposition to Disease
KW - Genetic Variation
KW - Genotype
KW - HSP72 Heat-Shock Proteins/genetics
KW - Humans
KW - Nuclear Proteins/genetics
KW - Polymorphism, Single Nucleotide/genetics
KW - Psychiatric Status Rating Scales
KW - Receptors, G-Protein-Coupled
KW - Schizophrenia/drug therapy
KW - Schizophrenic Psychology
U2 - 10.1016/j.euroneuro.2009.07.001
DO - 10.1016/j.euroneuro.2009.07.001
M3 - Journal article
C2 - 19643584
SN - 0924-977X
VL - 19
SP - 806
EP - 811
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
IS - 11
ER -