GWAS of Clinical Response in OCD
Umehara, Hidehiro Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Numata, Shusuke Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Nishi, Akira Tokushima University
Nakataki, Masahito Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Sumitani, Satsuki Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
genome-wide association study
Thesis or Dissertation
Selective serotonin reuptake inhibitors (SSRI) are established first-line pharmacological treatments for obsessive-compulsive disorder (OCD), while antipsychotics are used as an augmentation strategy for SSRI in OCD patients who have either no response or a partial response to SSRI treatment. The goal of the present study was to identify genetic variants and pathways that are associated with the long-term clinical response of OCD patients to SSRI or SSRI with antipsychotics.
We first performed a genome-wide association study of 96 OCD patients to examine genetic variants contributing to the response to SSRI or SSRI with antipsychotics. Subsequently, we conducted pathway-based analyses by using Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS) to examine the combined effects of genetic variants on the clinical response in OCD.
While we failed to detect specific genetic variants associated with clinical responses to SSRI or to SSRI with an atypical antipsychotic at genome-wide levels of significance, we identified 8 enriched pathways for the SSRI treatment response and 5 enriched pathways for the treatment response to SSRI with an antipsychotic medication. Notably, the calcium signaling pathway was identified in both treatment responses.
Our results provide novel insight into the molecular mechanisms underlying the variability in clinical response to SSRI and SSRI with antipsychotics in OCD patients.
本論文は, 著者Hidehiro Umeharaの学位論文として提出され, 学位審査・授与の対象となっている。
Copyright: © 2016 Umehara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Doctor of Medical Science
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