ArticleThe pharmacogenomics journal2012
Genome-wide association study of antipsychotic-induced QTc interval prolongation.
Article in The pharmacogenomics journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- A large genome-wide association study of QT interval length utilizing electronic health records.Genetics · 2022Pooled it
- Drug-gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval.The pharmacogenomics journal · 2014Pooled it
- Pharmacogenomic markers associated with drug-induced QT prolongation: a systematic review.PharmacogenomicsPooled it
- ATAD3B and SKIL polymorphisms associated with antipsychotic-induced QTc interval change in patients with schizophrenia: a genome-wide association study.Translational psychiatry · 2022Trial
- QTc prolongation in short-term treatment of schizophrenia patients: effects of different antipsychotics and genetic factors.European archives of psychiatry and clinical neuroscience · 2018Trial
- Genotypic variation in the SV2C gene impacts response to atypical antipsychotics the CATIE study.Schizophrenia research · 2013Trial
- Pharmacogenomic study of side-effects for antidepressant treatment options in STAR*D.Psychological medicine · 2012Trial
- Article
- Genetic risk factors for drug-induced long QT syndrome: findings from a large real-world case-control study.Pharmacogenomics · 2024Observational
- Knockout of the orphan membrane transporter Slc22a23 leads to a lean and hyperactive phenotype with a small hippocampal volume.PloS one · 2024Article
- CDK4/6 inhibitors: basics, pros, and major cons in breast cancer treatment with specific regard to cardiotoxicity - a narrative review.Therapeutic advances in medical oncology · 2023Review
- Pharmacogenomics for Prediction of Cardiovascular Toxicity: Landscape of Emerging Data in Breast Cancer Therapies.Cancers · 2022Review
- The genetics of drug-induced QT prolongation: evaluating the evidence for pharmacodynamic variants.Pharmacogenomics · 2022Review
- Computational estimates of annular diameter reveal genetic determinants of mitral valve function and disease.JCI insight · 2022Article
- Article
- Genetic and Molecular Aspects of Drug-Induced QT Interval Prolongation.International journal of molecular sciences · 2021Review
- QTc Interval Prolongation with Therapies Used to Treat Patients with Parkinson's Disease Psychosis: A Narrative Review.Neuropsychiatric disease and treatment · 2021Review
- Systems Biology Analysis Reveals Eight SLC22 Transporter Subgroups, Including OATs, OCTs, and OCTNs.International journal of molecular sciences · 2020Article
- Delineating significant genome-wide associations of variants with antipsychotic and antidepressant treatment response: implications for clinical pharmacogenomics.Human genomics · 2020Article
- Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
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 prolongation. SLC22A23 belongs to a family of organic ion transporters that shuttle a variety of compounds, including drugs, environmental toxins and endogenous metabolites, across the cell membrane. This gene is expressed in the heart and is integral in mouse heart development. The genes mediating antipsychotic-induced QT prolongation partially overlap with the genes affecting normal QT interval variation. However, some genes may also be unique for drug-induced prolongation. This study demonstrates the potential of GWAS to discover genes and pathways that mediate antipsychotic-induced QT prolongation.
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Registered trials
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