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

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

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 (MDD). While no SNP associations reached the genome-wide level of significance, 14 SNPs of interest...

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Main Authors: Ji, Yuan, Biernacka, Joanna M., Hebbring, Scott, Chai, Yubo, Jenkins, Gregory D., Batzler, Anthony, Snyder, Karen A., Drews, Maureen S., Desta, Zeruesenay, Flockhart, David, Mushiroda, Taisei, Kubo, Michiaki, Nakamura, Yusuke, Kamatani, Naoyuki, Schaid, Daniel, Weinshilboum, Richard M., Mrazek, David A.
Format: Online
Language:English
Published: 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941038/
id pubmed-3941038
recordtype oai_dc
spelling pubmed-39410382014-04-01 Pharmacogenomics of selective serotonin reuptake inhibitor treatment for major depressive disorder: genome-wide associations and functional genomics Ji, Yuan Biernacka, Joanna M. Hebbring, Scott Chai, Yubo Jenkins, Gregory D. Batzler, Anthony Snyder, Karen A. Drews, Maureen S. Desta, Zeruesenay Flockhart, David Mushiroda, Taisei Kubo, Michiaki Nakamura, Yusuke Kamatani, Naoyuki Schaid, Daniel Weinshilboum, Richard M. Mrazek, David A. Article 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 (MDD). While no SNP associations reached the genome-wide level of significance, 14 SNPs of interest were identified for functional analysis. The rs11144870 SNP in riboflavin kinase (RFK) gene on chromosome 9 was associated with eight week treatment response (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 eight 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 analytic strategy is to provide insights into the potential relevance of biologically plausible observed associations. 2012-08-21 2013-10 /pmc/articles/PMC3941038/ /pubmed/22907730 http://dx.doi.org/10.1038/tpj.2012.32 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Ji, Yuan
Biernacka, Joanna M.
Hebbring, Scott
Chai, Yubo
Jenkins, Gregory D.
Batzler, Anthony
Snyder, Karen A.
Drews, Maureen S.
Desta, Zeruesenay
Flockhart, David
Mushiroda, Taisei
Kubo, Michiaki
Nakamura, Yusuke
Kamatani, Naoyuki
Schaid, Daniel
Weinshilboum, Richard M.
Mrazek, David A.
spellingShingle Ji, Yuan
Biernacka, Joanna M.
Hebbring, Scott
Chai, Yubo
Jenkins, Gregory D.
Batzler, Anthony
Snyder, Karen A.
Drews, Maureen S.
Desta, Zeruesenay
Flockhart, David
Mushiroda, Taisei
Kubo, Michiaki
Nakamura, Yusuke
Kamatani, Naoyuki
Schaid, Daniel
Weinshilboum, Richard M.
Mrazek, David A.
Pharmacogenomics of selective serotonin reuptake inhibitor treatment for major depressive disorder: genome-wide associations and functional genomics
author_facet Ji, Yuan
Biernacka, Joanna M.
Hebbring, Scott
Chai, Yubo
Jenkins, Gregory D.
Batzler, Anthony
Snyder, Karen A.
Drews, Maureen S.
Desta, Zeruesenay
Flockhart, David
Mushiroda, Taisei
Kubo, Michiaki
Nakamura, Yusuke
Kamatani, Naoyuki
Schaid, Daniel
Weinshilboum, Richard M.
Mrazek, David A.
author_sort Ji, Yuan
title Pharmacogenomics of selective serotonin reuptake inhibitor treatment for major depressive disorder: genome-wide associations and functional genomics
title_short Pharmacogenomics of selective serotonin reuptake inhibitor treatment for major depressive disorder: genome-wide associations and functional genomics
title_full Pharmacogenomics of selective serotonin reuptake inhibitor treatment for major depressive disorder: genome-wide associations and functional genomics
title_fullStr Pharmacogenomics of selective serotonin reuptake inhibitor treatment for major depressive disorder: genome-wide associations and functional genomics
title_full_unstemmed Pharmacogenomics of selective serotonin reuptake inhibitor treatment for major depressive disorder: genome-wide associations and functional genomics
title_sort pharmacogenomics of selective serotonin reuptake inhibitor treatment for major depressive disorder: genome-wide associations and functional genomics
description 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 (MDD). While no SNP associations reached the genome-wide level of significance, 14 SNPs of interest were identified for functional analysis. The rs11144870 SNP in riboflavin kinase (RFK) gene on chromosome 9 was associated with eight week treatment response (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 eight 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 analytic strategy is to provide insights into the potential relevance of biologically plausible observed associations.
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941038/
_version_ 1612063790432518144

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