T52 - The Potential Role of Low Frequency And Rare Variants In Tardive Dyskinesia Genetics

Abstract

Background Tardive dyskinesia (TD) is a chronic, irreversible side effect of antipsychotic-treated schizophrenia patients TD occurrence is influenced by both clinical and demographic variables, as well as genetic factors. Contribution of common variants to TD susceptibility has been investigated in recent years, including by the genome-wide association study approach, but results are inconsistent. In order to discover the involvement of low frequency and rare variants in this phenotype, we implemented whole exome sequencing (WES) method. Methods We whole exome sequenced 20 Ashkenazi Jewish schizophrenia patients with severe TD, and 18 patients without any manifestation of TD (total AIMS score of zero) despite more than 10 years of exposure to antipsychotics. For prioritization, we concentrated on Loss of Function (LoF) rare variants. Results We were able to identify several interesting rare (1%-5%) and extremely rare ( Discussion WES may be implemented in pharmacogenetics studies of antipsychotics. Our preliminary results point to the role of low frequency and rare LoF variants in TD.