Genome-wide association study on antipsychotic-induced weight gain in the CATIE sample
| Autor: | Clement C. Zai, Arun K. Tiwari, J A Lieberman, Erika L. Nurmi, J.L. Kennedy, Vanessa F. Gonçalves, Eva J. Brandl, Jiangshan Jane Shen, Tamara Arenovich, Herbert Y. Meltzer, M Sanches, Daniel J. Müller, Nabilah I. Chowdhury |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Oncology medicine.medical_specialty Genotype Pharmacogenomic Variants medicine.medical_treatment Genome-wide association study Biology Weight Gain Bioinformatics Polymorphism Single Nucleotide Risk Assessment 03 medical and health sciences 0302 clinical medicine Risk Factors Polymorphism (computer science) Internal medicine Genetics medicine Humans Antipsychotic Randomized Controlled Trials as Topic Pharmacology Middle Aged United States Pharmacogenomic Testing 030227 psychiatry Europe Phenotype Pharmacogenomics Meta-analysis Cohort Schizophrenia Molecular Medicine Female medicine.symptom Carrier Proteins Weight gain 030217 neurology & neurosurgery Antipsychotic Agents Genome-Wide Association Study |
| Zdroj: | The Pharmacogenomics Journal. 16:352-356 |
| ISSN: | 1473-1150 1470-269X |
| Popis: | Antipsychotic-induced weight gain (AIWG) is a common side effect with a high genetic contribution. We reanalyzed genome-wide association study (GWAS) data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) selecting a refined subset of patients most suitable for AIWG studies. The final GWAS was conducted in N=189 individuals. The top polymorphisms were analyzed in a second cohort of N=86 patients. None of the single-nucleotide polymorphisms was significant at the genome-wide threshold of 5x10(-8). We observed interesting trends for rs9346455 (P=6.49x10(-6)) upstream of OGFRL1, the intergenic variants rs7336345 (P=1.31 × 10(-5)) and rs1012650 (P=1.47 × 10(-5)), and rs1059778 (P=1.49x10(-5)) in IBA57. In the second cohort, rs9346455 showed significant association with AIWG (P=0.005). The combined meta-analysis P-value for rs9346455 was 1.09 × 10(-7). Our reanalysis of the CATIE GWAS data revealed interesting new variants associated with AIWG. As the functional relevance of these polymorphisms is yet to be determined, further studies are needed.The Pharmacogenomics Journal advance online publication, 1 September 2015; doi:10.1038/tpj.2015.59. |
| Databáze: | OpenAIRE |
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