Lisoway Amanda J, Zai Gwyneth, Tiwari Arun K, Zai Clement C, Wigg Karen, Goncalves Vanessa, Zhang Danning, Freeman Natalie, Müller Daniel J, Kennedy James L, Richter Margaret A
Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Hum Psychopharmacol. 2018 Jul;33(4):e2659. doi: 10.1002/hup.2659. Epub 2018 Jun 28.
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.
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.
We did not observe a significant association between rs17162912 and SRI response (p = .32).
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.
最近一项针对强迫症（OCD）的全基因组关联研究（GWAS）报告称，在与5-羟色胺再摄取抑制剂（SRI）抗抑郁反应相关的果蝇派遣同源物1（DISP1）基因中发现了一个显著标记（Qin等人）。在这项GWAS之前，从未研究过DISP1与SRI反应之间的关联。我们试图通过研究112名欧洲白种人OCD患者样本中DISP1 rs17162912多态性与SRI反应之间的关联来重复GWAS的发现。
患者此前接受过自然治疗，依次使用多达6种不同的SRI，包括5种选择性SRI（氟西汀、氟伏沙明、舍曲林、帕罗西汀和西酞普兰）和1种SRI（氯米帕明）。对每个药物试验的反应进行回顾性评估，并使用临床总体印象改善量表将其分类为反应者或无反应者。采用Fisher精确检验来研究DISP1 rs17162912基因型分布与SRI反应之间的关系。
我们未观察到rs17162912与SRI反应之间存在显著关联（p = 0.32）。
这项重复研究不支持DISP1在预测OCD患者SRI反应中的作用；然而，原始GWAS与我们的研究之间的方法学差异，以及检验效能有限和次要等位基因频率较低，可能阻碍了重复研究的结果。
