A genome-wide association study of a sustained pattern of antidepressant response

J Psychiatr Res. 2013 Sep;47(9):1157-65. doi: 10.1016/j.jpsychires.2013.05.002. Epub 2013 May 30.


Genome-wide association studies (GWAS) have failed to replicate common genetic variants associated with antidepressant response, as defined using a single endpoint. Genetic influences may be discernible by examining individual variation between sustained versus unsustained patterns of response, which may distinguish medication effects from non-specific, or placebo responses to active medication. We conducted a GWAS among 1116 subjects with Major Depressive Disorder from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial who were characterized using Growth Mixture Modeling as showing a sustained versus unsustained pattern of clinical response over 12 weeks of treatment with citalopram. Replication analyses examined 585 subjects from the Genome-based Therapeutic Drugs for Depression (GENDEP) trial. The strongest association with sustained as opposed to unsustained response in STAR*D involved a single nucleotide polymorphism (SNP; rs10492002) within the acyl-CoA synthetase short-chain family member 3 gene (ACSS3, p-value=4.5×10(-6), odds ratio=0.61). No SNPs met our threshold for genome-wide significance. SNP data were available in GENDEP for 18 of the top 25 SNPs in STAR*D. The most replicable association was with SNP rs7816924 (p=0.008, OR=1.58); no SNP met the replication p-value threshold of 0.003. Joint analysis of these 18 SNPs resulted in the strongest signal coming from rs7816924 (p=2.11×10(-7)), which resides in chondroitin sulfate N-acetylgalactosaminyltransferase 1 gene (CSGALNACT1). An exploratory genetic pathway analysis revealed evidence for an involvement of the KEGG pathway of long-term potentiation (FDR=.02). Results suggest novel genetic associations to sustained response.

Keywords: Antidepressant; Citalopram; GENDEP; Genetics; Growth mixture modeling; STAR*D.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / therapeutic use*
  • Clinical Trials as Topic
  • Confidence Intervals
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / genetics*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Odds Ratio
  • Pharmacogenetics*
  • Polymorphism, Single Nucleotide / genetics*


  • Antidepressive Agents