A Genomewide Association Study of Citalopram Response in Major Depressive Disorder

Background Antidepressant response is likely influenced by genetic constitution, but the actual genes involved have yet to be determined. We have carried out a genomewide association study to determine whether common DNA variation influences antidepressant response. Methods Our sample is derived fro...

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Published in:	Biological psychiatry (1969) 2010-01, Vol.67 (2), p.133-138
Main Authors:	Garriock, Holly A, Kraft, Jeffrey B, Shyn, Stanley I, Peters, Eric J, Yokoyama, Jennifer S, Jenkins, Gregory D, Reinalda, Megan S, Slager, Susan L, McGrath, Patrick J, Hamilton, Steven P
Format:	Article
Language:	eng
Subjects:	ACCN1 Adult and adolescent clinical studies antidepressant Antidepressive Agents, Second-Generation - therapeutic use ARNTL Biological and medical sciences Bone Morphogenetic Protein 7 - genetics citalopram Citalopram - therapeutic use Cluster Analysis Depression Depressive Disorder, Major - drug therapy Depressive Disorder, Major - genetics Female Gene Frequency Genetic Predisposition to Disease Genetics Genome-Wide Association Study Genotype Humans Male Medical sciences Mood disorders Neuropharmacology Nuclear Receptor Subfamily 1, Group F, Member 1 - genetics Odds Ratio Pharmacogenetics Pharmacology. Drug treatments Polymorphism, Single Nucleotide - genetics Psychiatric Status Rating Scales Psychiatry Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychopharmacology Sex Factors STARD Statistics as Topic Treatment Outcome UBE3C Ubiquitin-Conjugating Enzymes - genetics
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Summary:	Background Antidepressant response is likely influenced by genetic constitution, but the actual genes involved have yet to be determined. We have carried out a genomewide association study to determine whether common DNA variation influences antidepressant response. Methods Our sample is derived from Level 1 participants in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, all treated with citalopram. Association for the response phenotype included 883 responders and 608 nonresponders. For the remission phenotype, 743 subjects that achieved remission were compared with 608 nonresponders. We used a subset of single nucleotide polymorphisms (SNPs; n = 430,198) from the Affymetrix 500K and 5.0 Human SNP Arrays, and association analysis was carried out after correcting for population stratification. Results We identified three SNPs associated with response with p values less than 1 × 10−5 near the UBE3C gene (rs6966038, p = 4.65 × 10−7 ), another 100 kb away from BMP7 (rs6127921, p = 3.45 × 10−6 ), and a third that is intronic in the RORA gene (rs809736, p = 8.19 × 10−6 ). These same SNPs were also associated with remission. Thirty-nine additional SNPs are of interest with p values ≤ .0001 for the response and remission phenotypes. Conclusions Although the findings reported here do not meet a genomewide threshold for significance, the regions identified from this study provide targets for independent replication and novel pathways to investigate mechanisms of antidepressant response. This study was not placebo controlled, making it possible that we are also observing associations to nonspecific aspects of drug treatment of depression.
ISSN:	0006-3223 1873-2402