Pharmacogenetic evaluation of a DISP1 gene variant in antidepressant treatment of obsessive-compulsive disorder

Hum Psychopharmacol. 2018 Jul;33(4):e2659. doi: 10.1002/hup.2659. Epub 2018 Jun 28.

Abstract

Objectives: A recent genome-wide association study (GWAS) in obsessive-compulsive disorder (OCD) reported a significant marker in the dispatched homolog 1 (Drosophila) gene (DISP1 gene) associated with serotonin reuptake inhibitor (SRI) antidepressant response (Qin et al., ). DISP1 has never been examined before in terms of association with SRI response until this GWAS. We attempt to replicate the GWAS finding by investigating the association of the DISP1 rs17162912 polymorphism with SRI response in our sample of 112 European Caucasian OCD patients.

Methods: Patients were previously treated naturalistically with up to 6 different SRIs sequentially, including 5 selective SRIs (fluoxetine, fluvoxamine, sertraline, paroxetine, and citalopram) and 1 SRI (clomipramine). Each medication trial was evaluated retrospectively for response and was rated categorically as either responder or nonresponder using the Clinical Global Impression-Improvement scale. Fisher's exact test was used to investigate the relationship between the DISP1 rs17162912 genotype distribution and SRI response.

Results: We did not observe a significant association between rs17162912 and SRI response (p = .32).

Conclusion: This replication study did not support the role of DISP1 in predicting SRI response in OCD; however, methodological differences between the original GWAS and our study, as well as limited power and low minor allele frequency, may have hindered replication.

Keywords: DISP1 gene; antidepressant/drug/treatment response; obsessive-compulsive disorder (OCD); pharmacogenetics.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / therapeutic use*
  • Female
  • Gene Frequency
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Obsessive-Compulsive Disorder / drug therapy*
  • Obsessive-Compulsive Disorder / genetics*
  • Polymorphism, Single Nucleotide*
  • Retrospective Studies
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Treatment Outcome
  • White People / genetics
  • Young Adult

Substances

  • Antidepressive Agents
  • Serotonin Uptake Inhibitors