scholarly journals Pathways analyses of schizophrenia GWAS focusing on known and novel drug targets

2016 ◽  
Author(s):  
H.A. Gaspar ◽  
G. Breen
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Drug Targets ◽  
Drug Repurposing ◽  
Channel Blockers ◽  
Gene Annotations ◽  
Genome Wide ◽  
Therapeutic Leads ◽  
Novel Drug ◽  
Novel Drug Targets

ABSTRACTUsing successful genome-wide association results in psychiatry for drug repurposing is an ongoing challenge. Databases collecting drug targets and gene annotations are growing and can be harnessed to shed a new light on psychiatric disorders. We used GWAS summary statistics from the Psychiatric Genetics Consortium (PGC) Schizophrenia working group and a repositioning model for schizophrenia by testing the enrichment of antipsychotics. As sample size increases, schizophrenia GWAS results show increasing enrichment for known antipsychotic drugs, selective calcium channel blockers, and antiepileptics. Each of these therapeutical classes targets different gene subnetworks. We identify 162 Bonferroni-significant druggable genes, and 128 FDR-significant biological pathways related to neurons, synapses, genic intolerance, membrane transport, epilepsy, and mental disorders. These results suggest that, in schizophrenia, current well-powered GWAS results can reliably detect known schizophrenia drugs and thus may hold considerable potential for the identification of new therapeutic leads. Moreover, antiepileptics and calcium channel blockers may provide repurposing opportunities. This study also reveals significant pathways in schizophrenia that were not identified previously, and provides a workflow for pathway analysis and drug repurposing using GWAS results.

scholarly journals Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics

2021 ◽  
Author(s):  
Max Lam ◽  
Chia-Yen Chen ◽  
Tian Ge ◽  
Yan Xia ◽  
David W. Hill ◽  
...  
Keyword(s):  
Drug Targets ◽  
Large Scale ◽  
Association Studies ◽  
Drug Repurposing ◽  
Genome Wide Association Studies ◽  
Data Set ◽  
Nootropic Drug ◽  
Gene Sets ◽  
Genome Wide ◽  
Novel Drug

AbstractBroad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify “druggable” targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing.

scholarly journals Pathway analysis of GWAS loci identifies novel drug targets and repurposing opportunities

2018 ◽  
Author(s):  
Deepali Jhamb ◽  
Michal Magid-Slav ◽  
Mark R. Hurle ◽  
Pankaj Agarwal
Keyword(s):  
Drug Discovery ◽  
Pathway Analysis ◽  
Drug Targets ◽  
Global Analysis ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
If Current ◽  
Novel Drug ◽  
Novel Drug Targets

AbstractGenome-wide association studies (GWAS) have made considerable progress and there is emerging evidence that genetics-based targets can lead to 28% more launched drugs. However, translating the results of GWAS for drug discovery remains challenging. We analyzed 1,589 GWAS across 1,456 protein interaction pathways to translate these often, imprecise genetic loci into therapeutic hypotheses for 182 diseases. We validate these pathway-based genetic targets by testing if current drug targets are enriched in the pathway space of the same indication. Remarkably, 30% of diseases have significantly more targets in these pathways than expected by chance; the comparable number for GWAS alone (without using pathway analysis) is zero. Although pathway analysis is routine for GWAS, this study shows that the routine analysis can often enrich for drug targets, by performing a systematic global analysis to translate genetic findings into therapeutic hypotheses for new drug discovery and repositioning opportunities for current drugs.

scholarly journals High-Throughput Analysis of Genome-Wide Receptor Tyrosine Kinase Expression in Human Cancers Identifies Potential Novel Drug Targets

2004 ◽  
Vol 10 (4) ◽  
pp. 1241-1249 ◽  
Author(s):  
Carsten Müller-Tidow ◽  
Joachim Schwäble ◽  
Björn Steffen ◽  
Nicola Tidow ◽  
Burkhardt Brandt ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
High Throughput ◽  
Receptor Tyrosine Kinase ◽  
Drug Targets ◽  
High Throughput Analysis ◽  
Throughput Analysis ◽  
Genome Wide ◽  
Kinase Expression ◽  
Novel Drug ◽  
Novel Drug Targets

scholarly journals Drug Repurposing Approach, Potential Drugs, and Novel Drug Targets for COVID-19 Treatment

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Zemene Demelash Kifle ◽  
Akeberegn Gorems Ayele ◽  
Engidaw Fentahun Enyew
Keyword(s):  
Drug Targets ◽  
Protein Targeting ◽  
Drug Repurposing ◽  
Structural Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Dipeptidyl Peptidase 4 ◽  
Novel Coronavirus ◽  
Novel Drug ◽  
Novel Drug Targets ◽  
Viral Enzyme

Novel coronavirus first appeared in Wuhan, China, in December 2019, and it speedily expanded globally. Some medications which are used to treat other diseases seem to be effective in treating COVID-19 even without explicit support. The existing drugs that are summarized in this review primarily focused on therapeutic agents that possessed activity against other RNA viruses such as MERS-CoV and SARS-CoV. Drug repurposing or repositioning is a promising field in drug discovery that identifies new therapeutic opportunities for existing drugs such as corticosteroids, RNA-dependent RNA polymerase inhibitors, interferons, protease inhibitors, ivermectin, melatonin, teicoplanin, and some others. A search for new drug/drug targets is underway. Thus, blocking coronavirus structural protein, targeting viral enzyme, dipeptidyl peptidase 4, and membrane fusion blocker (angiotensin-converting enzyme 2 and CD147 inhibitor) are major sites based on molecular targets for the management of COVID-19 infection. The possible impact of biologics for the management of COVID19 is promising and includes a wide variety of options such as cytokines, nucleic acid-based therapies targeting virus gene expression, bioengineered and vectored antibodies, and various types of vaccines. This review demonstrates that the available data are not sufficient to suggest any treatment for the eradication of COVID-19 to be used at the clinical level. This article aims to review the roles of existing drugs and drug targets for COVID-19 treatment.

Novel drug targets in 2019

2020 ◽  
Vol 19 (5) ◽  
pp. 300-300 ◽  
Author(s):  
Sorin Avram ◽  
Liliana Halip ◽  
Ramona Curpan ◽  
Tudor I. Oprea
Keyword(s):  
Drug Targets ◽  
Novel Drug ◽  
Novel Drug Targets
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