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QT prolongation is associated with increased risk of cardiac arrhythmias. Identifying the genetic variants that mediate antipsychotic-induced prolongation may help to minimize this risk, which might prevent the removal of efficacious drugs from the market. We performed candidate gene analysis and five drug-specific genome-wide association studies (GWASs) with 492K single-nucleotide polymorphisms to search for genetic variation mediating antipsychotic-induced QT prolongation in 738 schizophrenia patients from the Clinical Antipsychotic Trial of Intervention Effectiveness study. Our candidate gene study suggests the involvement of NOS1AP and NUBPL (P-values= 1.45× 10− 05 and 2.66× 10− 13, respectively). Furthermore, our top GWAS hit achieving genome-wide significance, defined as a Q-value< 0.10 (P-value= 1.54× 10− 7, Q-value= 0.07), located in SLC22A23, mediated the effects of quetiapine on …