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

• Published in: The pharmacogenomics journal Vol. 13; no. 5; pp. 456 - 463
• Main Authors: 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, M, Nakamura, Y, Kamatani, N, Schaid, D, Weinshilboum, R M, Mrazek, D A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2013; Nature Publishing Group
• Subjects: 631/208/191; 631/208/205/2138; 692/699/476/1414; 692/700/565/1436/434; Adult; Antidepressants; Biomedical and Life Sciences; Biomedicine; Care and treatment; Chromosome 10; Chromosome 9; Chromosomes, Human, Pair 10; Chromosomes, Human, Pair 9; Clinical outcomes; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - genetics; Depressive Disorder, Major - metabolism; Electrophoretic mobility; Female; G protein-coupled receptor kinase; G-Protein-Coupled Receptor Kinase 5 - genetics; Gene Expression; Genetic aspects; Genome-Wide Association Study - methods; Genomes; Genomics; Genomics - methods; Human Genetics; Humans; Identification and classification; Kinases; Major depressive disorder; Male; Mental depression; Oncology; original-article; Patient outcomes; Pharmacogenetics - methods; Pharmacogenomics; Pharmacotherapy; Phosphotransferases (Alcohol Group Acceptor) - genetics; Polymorphism, Single Nucleotide - genetics; Psychopharmacology; Remission; Reporter gene; Riboflavin; Riboflavin kinase; Serotonin - genetics; Serotonin - metabolism; Serotonin uptake inhibitors; Serotonin Uptake Inhibitors - therapeutic use; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Transcription; Transcription, Genetic; Treatment Outcome; GWA; SSRI; functional genomics; major depressive disorder; selective serotonin reuptake inhibitors; genome-wide association study
• ISSN: 1470-269X; 1473-1150; 1473-1150
• DOI: 10.1038/tpj.2012.32

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.