AUTHOR=O’Connell Kevin Sean , McGregor Nathaniel Wade , Emsley Robin , Seedat Soraya , Warnich Louise 

TITLE=The Potential Role of Regulatory Genes (DNMT3A, HDAC5, and HDAC9) in Antipsychotic Treatment Response in South African Schizophrenia Patients

JOURNAL=Frontiers in Genetics

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.00641

DOI=10.3389/fgene.2019.00641

ISSN=1664-8021

ABSTRACT=<p>Despite advances in pharmacogenetics, the majority of heritability for treatment response cannot be explained by common variation, suggesting that factors such as epigenetics may play a key role. Regulatory genes, such as those involved in DNA methylation and transcriptional repression, are therefore excellent candidates for investigating antipsychotic treatment response. This study explored the differential expression of regulatory genes between patients with schizophrenia (chronic and antipsychotic-naïve first-episode patients) and healthy controls in order to identify candidate genes for association with antipsychotic treatment response. Seven candidate differentially expressed genes were identified, and four variants within these genes were found to be significantly associated with treatment response (<italic>DNMT3A</italic> rs2304429, <italic>HDAC5</italic> rs11079983, and <italic>HDAC9</italic> rs1178119 and rs11764843). Further analyses revealed that two of these variants (rs2304429 and rs11079983) are predicted to alter the expression of specific genes (<italic>DNMT3A</italic>, <italic>ASB16</italic>, and <italic>ASB16-AS1</italic>) in brain regions previously implicated in schizophrenia and treatment response. These results may aid in the development of biomarkers for antipsychotic treatment response, as well as novel drug targets.</p>