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 |
| 巻 | 13 |
| 発行部数 | 5 |
| DOI | |
| 出版物ステータス | Published - 01-10-2013 |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Genetics
- Pharmacology
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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
TY - JOUR
T1 - Pharmacogenomics of selective serotonin reuptake inhibitor treatment for major depressive disorder
T2 - Genome-wide associations and functional genomics
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
Y1 - 2013/10/1
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84884592615&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884592615&partnerID=8YFLogxK
U2 - 10.1038/tpj.2012.32
DO - 10.1038/tpj.2012.32
M3 - Article
C2 - 22907730
AN - SCOPUS:84884592615
VL - 13
SP - 456
EP - 463
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
SN - 1470-269X
IS - 5
ER -