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Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies.

Publication ,  Journal Article
GENDEP Investigators, ; MARS Investigators, ; STAR*D Investigators,
Published in: Am J Psychiatry
February 2013

OBJECTIVE: Indirect evidence suggests that common genetic variation contributes to individual differences in antidepressant efficacy among individuals with major depressive disorder, but previous studies may have been underpowered to detect these effects. METHOD: A meta-analysis was performed on data from three genome-wide pharmacogenetic studies (the Genome-Based Therapeutic Drugs for Depression [GENDEP] project, the Munich Antidepressant Response Signature [MARS] project, and the Sequenced Treatment Alternatives to Relieve Depression [STAR*D] study), which included 2,256 individuals of Northern European descent with major depressive disorder, and antidepressant treatment outcomes were prospectively collected. After imputation, 1.2 million single-nucleotide polymorphisms were tested, capturing common variation for association with symptomatic improvement and remission after up to 12 weeks of antidepressant treatment. RESULTS: No individual association met a genome-wide threshold for statistical significance in the primary analyses. A polygenic score derived from a meta-analysis of GENDEP and MARS participants accounted for up to approximately 1.2% of the variance in outcomes in STAR*D, suggesting a weakly concordant signal distributed over many polymorphisms. An analysis restricted to 1,354 individuals treated with citalopram (STAR*D) or escitalopram (GENDEP) identified an intergenic region on chromosome 5 associated with early improvement after 2 weeks of treatment. CONCLUSIONS: Despite increased statistical power accorded by meta-analysis, the authors identified no reliable predictors of antidepressant treatment outcome, although they did identify modest, direct evidence that common genetic variation contributes to individual differences in antidepressant response.

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Published In

Am J Psychiatry

DOI

EISSN

1535-7228

Publication Date

February 2013

Volume

170

Issue

2

Start / End Page

207 / 217

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Remission Induction
  • Psychiatry
  • Psychiatric Status Rating Scales
  • Polymorphism, Single Nucleotide
  • Pharmacogenetics
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
 

Citation

APA
Chicago
ICMJE
MLA
NLM
GENDEP Investigators, ., MARS Investigators, ., & STAR*D Investigators, . (2013). Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies. Am J Psychiatry, 170(2), 207–217. https://doi.org/10.1176/appi.ajp.2012.12020237
GENDEP Investigators, C. R., C. R. MARS Investigators, and C. R. STAR*D Investigators. “Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies.Am J Psychiatry 170, no. 2 (February 2013): 207–17. https://doi.org/10.1176/appi.ajp.2012.12020237.
GENDEP Investigators, MARS Investigators, STAR*D Investigators. Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies. Am J Psychiatry. 2013 Feb;170(2):207–17.
GENDEP Investigators, C. R., et al. “Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies.Am J Psychiatry, vol. 170, no. 2, Feb. 2013, pp. 207–17. Pubmed, doi:10.1176/appi.ajp.2012.12020237.
GENDEP Investigators, MARS Investigators, STAR*D Investigators. Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies. Am J Psychiatry. 2013 Feb;170(2):207–217.
Journal cover image

Published In

Am J Psychiatry

DOI

EISSN

1535-7228

Publication Date

February 2013

Volume

170

Issue

2

Start / End Page

207 / 217

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Remission Induction
  • Psychiatry
  • Psychiatric Status Rating Scales
  • Polymorphism, Single Nucleotide
  • Pharmacogenetics
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study