@article{BiernackaSangkuhlJenkinsetal.2015, author = {Biernacka, J. M. and Sangkuhl, K. and Jenkins, G. and Whaley, R. M. and Barman, P. and Batzler, A. and Altman, R. B. and Arolt, V. and Brockm{\"o}ller, J. and Chen, C. H. and Domschke, K. and Hall-Flavin, D. K. and Hong, C. J. and Illi, A. and Ji, Y. and Kampman, O. and Kinoshita, T. and Leinonen, E. and Liou, Y. J. and Mushiroda, T. and Nonen, S. and Skime, M. K. and Wang, L. and Baune, B. T. and Kato, M. and Liu, Y. L. and Praphanphoj, V. and Stingl, J. C. and Tsai, S. J. and Kubo, M. and Klein, T. E. and Weinshilboum, R.}, title = {The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response}, series = {Translational Psychiatry}, volume = {5}, journal = {Translational Psychiatry}, number = {e553}, doi = {10.1038/tp.2015.47}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143223}, year = {2015}, 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. Top association results in the meta-analysis of response included single-nucleotide polymorphisms (SNPs) in the HPRTP4 (hypoxanthine phosphoribosyltransferase pseudogene 4)/VSTM5 (V-set and transmembrane domain containing 5) region, which approached genome-wide significance (P = 5.03E - 08) and 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.}, language = {en} }