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

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

Author information

1
Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, USA. amhunter@ucla.edu

Abstract

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

PMID:
23726668
PMCID:
PMC3710535
DOI:
10.1016/j.jpsychires.2013.05.002
[Indexed for MEDLINE]
Free PMC Article

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