A Genomewide Association Study of Citalopram Response in Major Depressive Disorder

Holly A. Garriock, Jeffrey B. Kraft, Stanley I. Shyn, Eric J. Peters, Jennifer S. Yokoyama, Gregory D. Jenkins, Megan S. Reinalda, Susan L. Slager, Patrick J. McGrath, Steven P. Hamilton

Research output: Contribution to journalArticlepeer-review

233 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)133-138
Number of pages6
JournalBiological psychiatry
Volume67
Issue number2
DOIs
StatePublished - Jan 15 2010

Keywords

  • ACCN1
  • ARNTL
  • Genetics
  • STAR*D
  • UBE3C
  • antidepressant
  • citalopram

ASJC Scopus subject areas

  • Biological Psychiatry

Fingerprint Dive into the research topics of 'A Genomewide Association Study of Citalopram Response in Major Depressive Disorder'. Together they form a unique fingerprint.

Cite this