Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Translating GWAS Findings Into Therapies For Depression And Anxiety Disorders: Drug Repositioning Using Gene-Set Analyses Reveals Enrichment Of Psychiatric Drug Classes

View ORCID ProfileHon-Cheong So, Alexandria Lau, Carlos Kwan-Long Chau, Sze-Yung Wong
doi: https://doi.org/10.1101/132563
Hon-Cheong So
1School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong
2KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research of Common Diseases, Kunming Zoology Institute of Zoology and The Chinese University of Hong Kong
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Hon-Cheong So
  • For correspondence: hcso@cuhk.edu.hk
Alexandria Lau
1School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carlos Kwan-Long Chau
1School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sze-Yung Wong
3Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Depression and anxiety disorders are the first and sixth leading cause of disability worldwide according to latest reports from the World Health Organization. Despite their high prevalence and the significant disability resulted, there are limited advances in new drug development. On the other hand, the advent of genome-wide association studies (GWAS) has greatly improved our understanding of the genetic basis underlying psychiatric disorders.

In this work we employed gene-set analyses of GWAS summary statistics for drug repositioning. We explored five related GWAS datasets, including two on major depressive disorder (MDD-PGC and MDD-CONVERGE, with the latter focusing on severe melancholic depression), one on anxiety disorders, and two on depressive symptoms and neuroticism in the population. We extracted gene-sets associated with each drug from DSigDB and examined their association with each GWAS phenotype. We also performed repositioning analyses on meta-analyzed GWAS data, integrating evidence from all related phenotypes.

Importantly, we showed that the repositioning hits are generally enriched for known psychiatric medications or those considered in clinical trials, except for MDD-PGC. Enrichment was seen for antidepressants and anxiolytics but also for antipsychotics. We also revealed new candidates or drug classes for repositioning, some of which were supported by experimental or clinical studies. For example, the top repositioning hit using meta-analyzed p-values was fendiline, which was shown to produce antidepressant-like effects in mouse models by inhibition of acid sphingomyelinase and reducing ceramide levels. Taken together, our findings suggest that human genomic data such as GWAS are useful in guiding drug discoveries for depression and anxiety disorders.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted September 08, 2017.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Translating GWAS Findings Into Therapies For Depression And Anxiety Disorders: Drug Repositioning Using Gene-Set Analyses Reveals Enrichment Of Psychiatric Drug Classes
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Translating GWAS Findings Into Therapies For Depression And Anxiety Disorders: Drug Repositioning Using Gene-Set Analyses Reveals Enrichment Of Psychiatric Drug Classes
Hon-Cheong So, Alexandria Lau, Carlos Kwan-Long Chau, Sze-Yung Wong
bioRxiv 132563; doi: https://doi.org/10.1101/132563
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Translating GWAS Findings Into Therapies For Depression And Anxiety Disorders: Drug Repositioning Using Gene-Set Analyses Reveals Enrichment Of Psychiatric Drug Classes
Hon-Cheong So, Alexandria Lau, Carlos Kwan-Long Chau, Sze-Yung Wong
bioRxiv 132563; doi: https://doi.org/10.1101/132563

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3701)
  • Biochemistry (7820)
  • Bioengineering (5695)
  • Bioinformatics (21343)
  • Biophysics (10603)
  • Cancer Biology (8206)
  • Cell Biology (11974)
  • Clinical Trials (138)
  • Developmental Biology (6786)
  • Ecology (10425)
  • Epidemiology (2065)
  • Evolutionary Biology (13908)
  • Genetics (9731)
  • Genomics (13109)
  • Immunology (8171)
  • Microbiology (20064)
  • Molecular Biology (7875)
  • Neuroscience (43171)
  • Paleontology (321)
  • Pathology (1282)
  • Pharmacology and Toxicology (2267)
  • Physiology (3363)
  • Plant Biology (7254)
  • Scientific Communication and Education (1316)
  • Synthetic Biology (2012)
  • Systems Biology (5550)
  • Zoology (1133)