Fine-mapping of antipsychotic response genome-wide association studies reveals novel regulatory mechanisms

Abstract

Aim: Noncoding variation has demonstrated regulatory effects on disease treatment outcomes. This study investigated the potential functionality of previously implicated noncoding variants on schizophrenia treatment response. Materials & methods: Predicted regulatory potential of variation identified from antipsychotic response genome-wide association studies was determined. Prioritized variants were assessed for association(s) with treatment outcomes in a South African first episode schizophrenia cohort (n = 103). Results: Bioinformatic and association results implicated a relationship between regulatory variants, expression of MANBA, COL9A2 and NFKB1, and treatment response. Three SNPs were associated with poor outcomes (rs230493: p = 1.88 × 10-6; rs3774959: p = 1.75 × 10-5; and rs230504: p = 1.48 × 10-4). Conclusion: This study has thoroughly investigated previous GWAS to pinpoint variants that may play a causal role in poor schizophrenia treatment outcomes, and provides potential candidate genes for further study in the field of antipsychotic response.