RESEARCH ARTICLE Pharmacogenetic evaluation of a DISP1 gene variant in antidepressant treatment of obsessive–compulsive disorder Amanda J. Lisoway 1,2* | Gwyneth Zai 1,3,4* | Arun K. Tiwari 1,4 | Clement C. Zai 1,4,5 | Karen Wigg 6 | Vanessa Goncalves 1,4 | Danning Zhang 1 | Natalie Freeman 1 | Daniel J. Müller 1,2,4,6 | James L. Kennedy 1,2,4† | Margaret A. Richter 2,4,7† 1 Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada 2 Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada 3 Mood and Anxiety Division, Centre for Addiction and Mental Health, Toronto, ON, Canada 4 Department of Psychiatry, University of Toronto, Toronto, ON, Canada 5 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada 6 Department of Pharmacology & Toxicology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada 7 The Frederick W. Thompson Anxiety Disorders Centre, Department of Psychiatry, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada Correspondence M.A. Richter, MD, FRCP(C), Head, Frederick W. Thompson Anxiety Disorders Centre, Dept. of Psychiatry, Sunnybrook Health Sciences Centre, Associate Professor of Psychiatry, University of Toronto, 2075 Bayview Avenue, Room FG42, Toronto, ON M4N 3M5, Canada. Email: peggy.richter@sunnybrook.ca Funding information Ministry of Research, Innovation, and Science; Ontario Mental Health Foundation; Genome Canada 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., 2015). 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, parox- etine, and citalopram) and 1 SRI (clomipramine). Each medication trial was evaluated retrospectively for response and was rated categorically as either responder or nonre- sponder 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 antidepressant/drug/treatment response, DISP1 gene, obsessive–compulsive disorder (OCD), pharmacogenetics 1 | INTRODUCTION Obsessive–compulsive disorder (OCD) is a chronic and debilitating psychiatric disorder that is characterized by obsessions (i.e., intrusive unwanted thoughts, images, or urges that result in distressing anxiety) and compulsions (i.e., repetitive behaviors which are aimed at reducing * These authors are co‐first authors on this manuscript. † These authors are co‐senior authors on this manuscript. Received: 12 September 2017 Revised: 17 January 2018 Accepted: 9 April 2018 DOI: 10.1002/hup.2659 Hum Psychopharmacol Clin Exp. 2018;e2659. https://doi.org/10.1002/hup.2659 © 2018 John Wiley & Sons, Ltd. wileyonlinelibrary.com/journal/hup 1 of 6