Investigation of epistasis between DAOA and 5HTR1A variants on clinical outcomes in patients with schizophrenia

Abstract

Purpose: In two recent studies of our group, rs10042486, a single-nucleotide polymorphism (SNP) within 5HTR1A, and rs7139958, a SNP within the d-amino acid oxidase activator (DAOA) were found to be associated with clinical improvement, as detected by the positive symptom subscale of the Positive and Negative Symptoms Scale (PANSS) in a sample 221 Korean schizophrenia patients treated with various antipsychotics. Methods: The existence of possible epistatic interactions between rs10042486 and rs7139958 influencing PANSS-positive subscale improvement scores in the same sample was investigated. Results: No significant epistatic interaction was observed. Furthermore, the independent associations observed between rs10042486, rs7139958, and PANSS-positive subscale improvement scores in earlier studies were no longer significant when they were included in our model. Conclusion: Although limited by some methodological shortcomings, our results preliminarily point to the possibility that positive genetic associations observed in some samples could not be replicated in different samples because of the existence of consistent differences in the genotype frequencies of other genetic polymorphisms that epistatically interact with the specific variants under investigation in a given study. © Copyright 2013, Mary Ann Liebert, Inc.