The International SSRI Pharmacogenomics Consortium (ISPC)

A genome-wide association study of antidepressant treatment response

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 & 12 others S. Nonen, M. K. Skime, L. Wang, B. T. Baune, M. Kato, Y. L. Liu, V. Praphanphoj, J. C. Stingl, S. J. Tsai, Michiaki Kubo, T. E. Klein, R. Weinshilboum

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article numberA047
JournalTranslational psychiatry
Volume5
Issue number4
DOIs
Publication statusPublished - 26-05-2015

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Genome-Wide Association Study
Pharmacogenetics
Serotonin Uptake Inhibitors
Antidepressive Agents
Depression
Single Nucleotide Polymorphism
Meta-Analysis
Genome
Neuregulin-1
Genes
Hypoxanthine Phosphoribosyltransferase
Pseudogenes
Major Depressive Disorder
Therapeutics
Research
Mental Disorders
Schizophrenia
Pharmacogenomic Testing
Brain

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

Cite this

Biernacka, J. M., Sangkuhl, K., Jenkins, G., Whaley, R. M., Barman, P., Batzler, A., ... Weinshilboum, R. (2015). The International SSRI Pharmacogenomics Consortium (ISPC): A genome-wide association study of antidepressant treatment response. Translational psychiatry, 5(4), [A047]. https://doi.org/10.1038/tp.2015.47
Biernacka, J. M. ; Sangkuhl, K. ; Jenkins, G. ; Whaley, R. M. ; Barman, P. ; Batzler, A. ; Altman, R. B. ; Arolt, V. ; Brockmöller, J. ; Chen, C. H. ; Domschke, K. ; Hall-Flavin, D. K. ; Hong, C. J. ; Illi, A. ; Ji, Y. ; Kampman, O. ; Kinoshita, T. ; Leinonen, E. ; Liou, Y. J. ; Mushiroda, T. ; Nonen, S. ; Skime, M. K. ; Wang, L. ; Baune, B. T. ; Kato, M. ; Liu, Y. L. ; Praphanphoj, V. ; Stingl, J. C. ; Tsai, S. J. ; Kubo, Michiaki ; Klein, T. E. ; Weinshilboum, R. / The International SSRI Pharmacogenomics Consortium (ISPC) : A genome-wide association study of antidepressant treatment response. In: Translational psychiatry. 2015 ; Vol. 5, No. 4.
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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.",
author = "Biernacka, {J. M.} and K. Sangkuhl and G. Jenkins and Whaley, {R. M.} and P. Barman and A. Batzler and Altman, {R. B.} and V. Arolt and J. Brockm{\"o}ller and Chen, {C. H.} and K. Domschke and Hall-Flavin, {D. K.} and Hong, {C. J.} and A. Illi and Y. Ji and O. Kampman and T. Kinoshita and E. Leinonen and Liou, {Y. J.} and T. Mushiroda and S. Nonen and Skime, {M. K.} and L. Wang and Baune, {B. T.} and M. Kato and Liu, {Y. L.} and V. Praphanphoj and Stingl, {J. C.} and Tsai, {S. J.} and Michiaki Kubo and Klein, {T. E.} and R. Weinshilboum",
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Biernacka, JM, Sangkuhl, K, Jenkins, G, Whaley, RM, Barman, P, Batzler, A, Altman, RB, Arolt, V, Brockmöller, J, Chen, CH, Domschke, K, Hall-Flavin, DK, Hong, CJ, Illi, A, Ji, Y, Kampman, O, Kinoshita, T, Leinonen, E, Liou, YJ, Mushiroda, T, Nonen, S, Skime, MK, Wang, L, Baune, BT, Kato, M, Liu, YL, Praphanphoj, V, Stingl, JC, Tsai, SJ, Kubo, M, Klein, TE & Weinshilboum, R 2015, 'The International SSRI Pharmacogenomics Consortium (ISPC): A genome-wide association study of antidepressant treatment response', Translational psychiatry, vol. 5, no. 4, A047. https://doi.org/10.1038/tp.2015.47

The International SSRI Pharmacogenomics Consortium (ISPC) : A genome-wide association study of antidepressant treatment response. / Biernacka, J. M.; Sangkuhl, K.; Jenkins, G.; Whaley, R. M.; Barman, P.; Batzler, A.; Altman, R. B.; Arolt, V.; Brockmöller, J.; Chen, C. H.; Domschke, K.; Hall-Flavin, D. K.; Hong, C. J.; Illi, A.; Ji, Y.; Kampman, O.; Kinoshita, T.; Leinonen, E.; Liou, Y. J.; Mushiroda, T.; Nonen, S.; Skime, M. K.; Wang, L.; Baune, B. T.; Kato, M.; Liu, Y. L.; Praphanphoj, V.; Stingl, J. C.; Tsai, S. J.; Kubo, Michiaki; Klein, T. E.; Weinshilboum, R.

In: Translational psychiatry, Vol. 5, No. 4, A047, 26.05.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The International SSRI Pharmacogenomics Consortium (ISPC)

T2 - A genome-wide association study of antidepressant treatment response

AU - Biernacka, J. M.

AU - Sangkuhl, K.

AU - Jenkins, G.

AU - Whaley, R. M.

AU - Barman, P.

AU - Batzler, A.

AU - Altman, R. B.

AU - Arolt, V.

AU - Brockmöller, J.

AU - Chen, C. H.

AU - Domschke, K.

AU - Hall-Flavin, D. K.

AU - Hong, C. J.

AU - Illi, A.

AU - Ji, Y.

AU - Kampman, O.

AU - Kinoshita, T.

AU - Leinonen, E.

AU - Liou, Y. J.

AU - Mushiroda, T.

AU - Nonen, S.

AU - Skime, M. K.

AU - Wang, L.

AU - Baune, B. T.

AU - Kato, M.

AU - Liu, Y. L.

AU - Praphanphoj, V.

AU - Stingl, J. C.

AU - Tsai, S. J.

AU - Kubo, Michiaki

AU - Klein, T. E.

AU - Weinshilboum, R.

PY - 2015/5/26

Y1 - 2015/5/26

N2 - 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.

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