scholarly journals Microbial Genome-Wide Association Studies: Lessons from Human GWAS

2016 ◽  
Author(s):  
Robert A. Power ◽  
Julian Parkhill ◽  
Tulio de Oliveira
Keyword(s):  
Disease Transmission ◽  
Drug Targets ◽  
Association Studies ◽  
Genome Wide Association ◽  
Microbial Genome ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Disease Aetiology ◽  
Number Of Microorganisms ◽  
Potential Drug Targets

AbstractThe reduced costs of sequencing have led to the availability of whole genome sequences for a large number of microorganisms, enabling the application of microbial genome wide association studies (GWAS). Given the successes of human GWAS in understanding disease aetiology and identifying potential drug targets, microbial GWAS is likely to further advance our understanding of infectious diseases. By building on the success of GWAS, microbial GWAS have the potential to rapidly provide important insights into pressing global health problems, such as antibiotic resistance and disease transmission. In this review, we outline the methodologies of GWAS, the state of the field of microbial GWAS today, and how lessons from GWAS can direct the future of the field.

scholarly journals Current Affairs of Microbial Genome-Wide Association Studies: Approaches, Bottlenecks and Analytical Pitfalls

2020 ◽  
Vol 10 ◽  
Author(s):  
James Emmanuel San ◽  
Shakuntala Baichoo ◽  
Aquillah Kanzi ◽  
Yumna Moosa ◽  
Richard Lessells ◽  
...  
Keyword(s):  
Association Studies ◽  
Genome Wide Association ◽  
Microbial Genome ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Current Affairs

Identifying Novel Psoriatic Disease Drug Targets Using a Genetics-Based Priority Index Pipeline

2021 ◽  
pp. 247553032110260
Author(s):  
Audrey Bui ◽  
Jared Liu ◽  
Julie Hong ◽  
Edward Hadeler ◽  
Megan Mosca ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Drug Targets ◽  
Association Studies ◽  
Therapeutic Targets ◽  
Genome Wide Association Studies ◽  
Priority Index ◽  
Psoriatic Disease ◽  
Genome Wide ◽  
Pathway Crosstalk ◽  
Potential Drug Targets

Background: Despite numerous genome-wide association studies conducted in psoriasis and psoriatic arthritis, only a small fraction of the identified genes has been therapeutically targeted. Objective: We sought to identify and analyze potential therapeutic targets for psoriasis and psoriatic arthritis (PsA) using the priority index (Pi), a genetics-dependent drug target prioritization approach. Methods: Significant genetic variants from GWAS for psoriasis, PsA, and combined psoriatic disease were annotated and run through the Pi pipeline. Potential drug targets were identified based on genomic predictors, annotation predictors, pathway enrichment, and pathway crosstalk. Results: Several gene targets were identified for psoriasis and PsA that demonstrated biological associations to their respective diseases. Some are currently being explored as potential therapeutic targets (i.e. ICAM1, NF-kB, REV3 L, ADRA1B for psoriasis; CCL11 for PsA); others have not yet been investigated (i.e. LNPEP, LCE3 for psoriasis; UBLCP1 for PsA). Additionally, many nodal points of potential intervention were identified as promising therapeutic targets. Of these, some are currently being studied such as TYK2 for psoriasis, and others have yet to be explored (i.e. PPP2CA, YAP1, PI3 K, AKT, FOXO1, RELA, CSF2, IFNGR1, IFNGR2 for psoriasis; GNAQ, PLCB1, GNAI2 for PsA). Conclusion: Through Pi, we identified data-driven candidate therapeutic gene targets and pathways for psoriasis and PsA. Given the sparse PsA specific genetic studies and PsA specific drug targets, this analysis could prove to be particularly valuable in the pipeline for novel psoriatic therapies.

scholarly journals Microbial genome-wide association studies: lessons from human GWAS

2016 ◽  
Vol 18 (1) ◽  
pp. 41-50 ◽  
Author(s):  
Robert A. Power ◽  
Julian Parkhill ◽  
Tulio de Oliveira
Keyword(s):  
Association Studies ◽  
Genome Wide Association ◽  
Microbial Genome ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Genetic cross-disorder analysis in psychiatry: from methodology to clinical utility

2019 ◽  
Vol 216 (5) ◽  
pp. 246-249 ◽  
Author(s):  
Dick Schijven ◽  
Jan H. Veldink ◽  
Jurjen J. Luykx
Keyword(s):  
Psychiatric Disorders ◽  
Clinical Utility ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Disease Aetiology ◽  
Genetic Cross

SummaryGenome-wide association studies have uncovered hundreds of loci associated with psychiatric disorders. Cross-disorder studies are among the prime ramifications of such research. Here, we discuss the methodology of the most widespread methods and their clinical utility with regard to diagnosis, prediction, disease aetiology and treatment in psychiatry.

Using Human Genetics to Understand Mechanisms in Ischemic Stroke Outcome: From Early Brain Injury to Long-Term Recovery

Stroke ◽  
2021 ◽  
Author(s):  
Jin-Moo Lee ◽  
Israel Fernandez-Cadenas ◽  
Arne G. Lindgren
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Early Brain Injury ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Stroke Outcome ◽  
Genome Wide

There is a critical need to elucidate molecular mechanisms underlying brain injury, repair, and recovery following ischemic stroke—a global health problem with major social and economic impact. Despite 5 decades of intensive research, there are no widely accepted neuroprotective drugs that mitigate ischemic brain injury, or neuroreparative drugs, or personalized approaches that guide therapies to enhance recovery. We here explore novel reverse translational approaches that will complement traditional forward translational methods in identifying mechanisms relevant to human stroke outcome. Although genome-wide association studies have yielded over 30 genetic loci that influence ischemic stroke risk, only a few genome-wide association studies have been performed for stroke outcome. We discuss important considerations for genetic studies of ischemic stroke outcome—including carefully designed phenotypes that capture injury/recovery mechanisms, anchored in time to stroke onset. We also address recent genome-wide association studies that provide insight into mechanisms underlying brain injury and repair. There are several ongoing initiatives exploring genomic associations with novel phenotypes related to stroke outcome. To improve the understanding of the genetic architecture of ischemic stroke outcome, larger studies using standardized phenotypes, preferably embedded in standard-of-care measures, are needed. Novel techniques beyond genome-wide association studies—including exploiting informatics, multi-omics, and novel analytics—promise to uncover genetic and molecular pathways from which drug targets and other new interventions may be identified.

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