The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
Year: 2015
Type: article
Study design: Observational Study
Abstract: Response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably between patients. The International SSRI Pharmacogenomics Consortium (ISPC) was formed with the primary goal of identifying genetic variation that may contribute to response to SSRI treatment of major depressive disorder. A genome-wide association study of 4-week treatment outcomes, measured using the 17-item Hamilton Rating Scale for Depression (HRSD-17), was performed using data from 865 subjects from seven sites. The primary outcomes were percent change in HRSD-17 score and response, defined as at least 50% reduction in HRSD-17. Data from two prior studies, the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study (PGRN-AMPS) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, were used for replication, and a meta-analysis of the three studies was performed (N=2394). Although many top association signals in the ISPC analysis map to interesting candidate genes, none were significant at the genome-wide level and the associations were not replicated using PGRN-AMPS and STAR*D data. The top association result in the meta-analysis of response represents SNPs 5′ upstream of the neuregulin-1 gene, NRG1 (P = 1.20E - 06). NRG1 is involved in many aspects of brain development, including neuronal maturation and variations in this gene have been shown to be associated with increased risk for mental disorders, particularly schizophrenia. Replication and functional studies of these findings are warranted.
Source: Translational Psychiatry
DOI: 10.1038/tp.2015.47
Authors: J M Biernacka, K Sangkuhl, G Jenkins, R M Whaley, P Barman, A Batzler, R B Altman, V Arolt, J Brockmöller, C H Chen, K Domschke, D K Hall-Flavin, C J Hong, A Illi, Y Ji, O Kampman, T Kinoshita, E Leinonen, Y J Liou, T Mushiroda, S Nonen, M K Skime, L Wang, B T Baune, M Kato, Y L Liu, V Praphanphoj, J C Stingl, S J Tsai, M Kubo, T E Klein, R Weinshilboum
Institutions: Mayo Clinic, Stanford University, University of Münster, University of Göttingen, Taipei Medical University-Shuang Ho Hospital, Taipei Medical University, University of Würzburg, Taipei Veterans General Hospital, National Yang Ming University, University of Tampere, Tampere University, Kansai Medical University, Tampere University Hospital, RIKEN Center for Integrative Medical Sciences, Hyogo University of Health Sciences, The University of Adelaide, National Health Research Institutes, Ministry of Public Health, Rajanukul Institute, Federal Institute for Drugs and Medical Devices
Language: English
Subfield: Pharmacology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,290
Funders: Thailand Center of Excellence for Life Sciences, Georgia Clinical and Translational Science Alliance, National Science Council, Thailand Research Fund, National Health Research Institutes, SENSHIN Medical Research Foundation, Tays, National Center for Genetic Engineering and Biotechnology, National Institutes of Health, Japan Society for the Promotion of Science, RIKEN, National Institute of General Medical Sciences, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G2264161801, G2370046335, G2405154935, G2545453578, G3006427632, G3041859643, G3148738089, PharmGKB: pharmacogenomics knowledge for precision medicine, G3254424250, G3446974707, G3668099937, G3886166795, Pharmacogenetics of Phase II Drug Metabolizing Enzymes, G4096800868, G4512846435, G5029307239, G5096183676, Inherited Variations In Drug Metabolizing Enzymes, G5599776357, G5671986908, G5909121220, G5916874944, G6936795642, G7619305095, G8137986288, G8648933450, Mayo Clinic Center for Translational Science Activities, G9000199262, G9000203062, G9000258299
OpenAlex ID: W2074495846