Pharmacogenomics of selective serotonin reuptake inhibitor treatment for major depressive disorder: Genome-wide associations and functional genomics

Y. Ji, J. M. Biernacka, S. Hebbring, Y. Chai, G. D. Jenkins, A. Batzler, K. A. Snyder, M. S. Drews, Z. Desta, D. Flockhart, T. Mushiroda, Michiaki Kubo, Y. Nakamura, N. Kamatani, D. Schaid, R. M. Weinshilboum, D. A. Mrazek

研究成果: Article

39 引用 (Scopus)

抄録

A genome-wide association (GWA) study of treatment outcomes (response and remission) of selective serotonin reuptake inhibitors (SSRIs) was conducted using 529 subjects with major depressive disorder. While no SNP associations reached the genome-wide level of significance, 14 SNPs of interest were identified for functional analysis. The rs11144870 SNP in the riboflavin kinase (RFK) gene on chromosome 9 was associated with 8-week treatment response (odds ratio (OR)=0.42, P=1.04 × 10 -6). The rs915120 SNP in the G protein-coupled receptor kinase 5 (GRK5) gene on chromosome 10 was associated with 8-week remission (OR=0.50, P=1.15 × 10 -5). Both SNPs were shown to influence transcription by a reporter gene assay and to alter nuclear protein binding using an electrophoretic mobility shift assay. This report represents an example of joining functional genomics with traditional GWA study results derived from a GWA analysis of SSRI treatment outcomes. The goal of this analytical strategy is to provide insights into the potential relevance of biologically plausible observed associations.

元の言語English
ページ(範囲)456-463
ページ数8
ジャーナルPharmacogenomics Journal
13
発行部数5
DOI
出版物ステータスPublished - 01-10-2013

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Pharmacogenetics
Major Depressive Disorder
Serotonin Uptake Inhibitors
Genomics
Single Nucleotide Polymorphism
Genome
Genome-Wide Association Study
riboflavin kinase
G-Protein-Coupled Receptor Kinase 5
Odds Ratio
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 9
Electrophoretic Mobility Shift Assay
Nuclear Proteins
Reporter Genes
Protein Binding
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Pharmacology

これを引用

Ji, Y. ; Biernacka, J. M. ; Hebbring, S. ; Chai, Y. ; Jenkins, G. D. ; Batzler, A. ; Snyder, K. A. ; Drews, M. S. ; Desta, Z. ; Flockhart, D. ; Mushiroda, T. ; Kubo, Michiaki ; Nakamura, Y. ; Kamatani, N. ; Schaid, D. ; Weinshilboum, R. M. ; Mrazek, D. A. / Pharmacogenomics of selective serotonin reuptake inhibitor treatment for major depressive disorder : Genome-wide associations and functional genomics. :: Pharmacogenomics Journal. 2013 ; 巻 13, 番号 5. pp. 456-463.
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abstract = "A genome-wide association (GWA) study of treatment outcomes (response and remission) of selective serotonin reuptake inhibitors (SSRIs) was conducted using 529 subjects with major depressive disorder. While no SNP associations reached the genome-wide level of significance, 14 SNPs of interest were identified for functional analysis. The rs11144870 SNP in the riboflavin kinase (RFK) gene on chromosome 9 was associated with 8-week treatment response (odds ratio (OR)=0.42, P=1.04 × 10 -6). The rs915120 SNP in the G protein-coupled receptor kinase 5 (GRK5) gene on chromosome 10 was associated with 8-week remission (OR=0.50, P=1.15 × 10 -5). Both SNPs were shown to influence transcription by a reporter gene assay and to alter nuclear protein binding using an electrophoretic mobility shift assay. This report represents an example of joining functional genomics with traditional GWA study results derived from a GWA analysis of SSRI treatment outcomes. The goal of this analytical strategy is to provide insights into the potential relevance of biologically plausible observed associations.",
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Ji, Y, Biernacka, JM, Hebbring, S, Chai, Y, Jenkins, GD, Batzler, A, Snyder, KA, Drews, MS, Desta, Z, Flockhart, D, Mushiroda, T, Kubo, M, Nakamura, Y, Kamatani, N, Schaid, D, Weinshilboum, RM & Mrazek, DA 2013, 'Pharmacogenomics of selective serotonin reuptake inhibitor treatment for major depressive disorder: Genome-wide associations and functional genomics', Pharmacogenomics Journal, 巻. 13, 番号 5, pp. 456-463. https://doi.org/10.1038/tpj.2012.32

Pharmacogenomics of selective serotonin reuptake inhibitor treatment for major depressive disorder : Genome-wide associations and functional genomics. / Ji, Y.; Biernacka, J. M.; Hebbring, S.; Chai, Y.; Jenkins, G. D.; Batzler, A.; Snyder, K. A.; Drews, M. S.; Desta, Z.; Flockhart, D.; Mushiroda, T.; Kubo, Michiaki; Nakamura, Y.; Kamatani, N.; Schaid, D.; Weinshilboum, R. M.; Mrazek, D. A.

:: Pharmacogenomics Journal, 巻 13, 番号 5, 01.10.2013, p. 456-463.

研究成果: Article

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T1 - Pharmacogenomics of selective serotonin reuptake inhibitor treatment for major depressive disorder

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AU - Ji, Y.

AU - Biernacka, J. M.

AU - Hebbring, S.

AU - Chai, Y.

AU - Jenkins, G. D.

AU - Batzler, A.

AU - Snyder, K. A.

AU - Drews, M. S.

AU - Desta, Z.

AU - Flockhart, D.

AU - Mushiroda, T.

AU - Kubo, Michiaki

AU - Nakamura, Y.

AU - Kamatani, N.

AU - Schaid, D.

AU - Weinshilboum, R. M.

AU - Mrazek, D. A.

PY - 2013/10/1

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N2 - A genome-wide association (GWA) study of treatment outcomes (response and remission) of selective serotonin reuptake inhibitors (SSRIs) was conducted using 529 subjects with major depressive disorder. While no SNP associations reached the genome-wide level of significance, 14 SNPs of interest were identified for functional analysis. The rs11144870 SNP in the riboflavin kinase (RFK) gene on chromosome 9 was associated with 8-week treatment response (odds ratio (OR)=0.42, P=1.04 × 10 -6). The rs915120 SNP in the G protein-coupled receptor kinase 5 (GRK5) gene on chromosome 10 was associated with 8-week remission (OR=0.50, P=1.15 × 10 -5). Both SNPs were shown to influence transcription by a reporter gene assay and to alter nuclear protein binding using an electrophoretic mobility shift assay. This report represents an example of joining functional genomics with traditional GWA study results derived from a GWA analysis of SSRI treatment outcomes. The goal of this analytical strategy is to provide insights into the potential relevance of biologically plausible observed associations.

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