EW_dmGWAS: edge-weighted dense module search for genome-wide association studies and gene expression profiles

SummaryHuman gene expression profiles have emerged as an effective model system for the dissection of quantitative genetic traits. Peripheral blood and transformed lymphoblasts are particularly attractive for their ready availability and repeatability, respectively, and the advent of relatively inexpensive genotyping and microarray analysis technologies has facilitated genome-wide association for transcript abundance in numerous settings. Thousands of genes have been shown to harbour regulatory polymorphisms that have large local effects on transcription, explaining 20% or more of the variance in many cases, but the focus on such results obscures the reality that the vast majority of the genetic component of transcriptional variance remains to be ascertained. This mini-review surveys the inferences derived from genome-wide association studies (GWAS) for gene expression to date, and discusses some of the issues we face in finding the remainder of the heritability and understanding how environmental and genetic regulatory factors orchestrate the highly structured architecture of transcriptional variation.

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TWENTY-FOUR GENES ARE UPREGULATED IN PATIENTS WITH HYPOSPADIAS

Balkan Journal of Medical Genetics ◽

10.2478/bjmg-2013-0030 ◽

2013 ◽

Vol 16 (2) ◽

pp. 39-43 ◽

Cited By ~ 6

Author(s):

R. Karabulut ◽

Z. Turkyilmaz ◽

K. Sonmez ◽

G. Kumas ◽

Sg. Ergun ◽

...

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Association Studies ◽

Gene Expression Profiles ◽

Ventral Surface ◽

Genome Wide Association Studies ◽

Expression Array ◽

Large Patient ◽

Expression Studies ◽

Genome Wide

ABSTRACT Hypospadias is a congenital hypoplasia of the penis, with displacement of the urethral opening along the ventral surface, and has been reported to be one of the most common congenital anomalies, occurring in approximately 1:250 to 1:300 live births. As hypospadias is reported to be an easily diagnosed malformation at the crossroads of genetics and environment, it is important to study the genetic component in order to elucidate its etiology. In this study, the gene expression profiles both in human hypospadias tissues and normal penile tissues were studied by Human Gene Expression Array. Twentyfour genes were found to be upregulated. Among these, ATF3 and CYR61 have been reported previously. Other genes that have not been previously reported were also found to be upregulated: BTG2, CD69, CD9, DUSP1, EGR1, EIF4A1, FOS, FOSB, HBEGF, HNRNPUL1, IER2, JUN, JUNB, KLF2, NR4A1, NR4A2, PTGS2, RGS1, RTN4, SLC25A25, SOCS3 and ZFP36 (p <0.05). Further studies including genome-wide association studies (GWAS) with expression studies in a large patient group will help us for identifiying the candidate gene(s) in the etiology of hypospadias

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Faculty Opinions recommendation of Meta-Analysis of Genome-Wide Association Studies and Network Analysis-Based Integration with Gene Expression Data Identify New Suggestive Loci and Unravel a Wnt-Centric Network Associated with Dupuytren's Disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726582766.793522025 ◽

2016 ◽

Author(s):

Rik Lories

Keyword(s):

Gene Expression ◽

Network Analysis ◽

Gene Expression Data ◽

Association Studies ◽

Meta Analysis ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Expression Data ◽

Dupuytren's Disease ◽

Genome Wide

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Gene expression levels as endophenotypes in genome-wide association studies of Alzheimer disease

Neurology ◽

10.1212/wnl.0b013e3181d07654 ◽

2010 ◽

Vol 74 (6) ◽

pp. 480-486 ◽

Cited By ~ 24

Author(s):

F. Zou ◽

M. M. Carrasquillo ◽

V. S. Pankratz ◽

O. Belbin ◽

K. Morgan ◽

...

Keyword(s):

Gene Expression ◽

Alzheimer Disease ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Expression Levels ◽

Genome Wide ◽

Gene Expression Levels

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Prioritization of SNPs for genome-wide association studies using an interaction model of genetic variation, gene expression, and trait variation

Molecules and Cells ◽

10.1007/s10059-012-2264-7 ◽

2012 ◽

Vol 33 (4) ◽

pp. 351-361 ◽

Cited By ~ 1

Author(s):

Hyojung Paik ◽

Junho Kim ◽

Sunjae Lee ◽

Hyoung-Sam Heo ◽

Cheol-Goo Hur ◽

...

Keyword(s):

Gene Expression ◽

Genetic Variation ◽

Association Studies ◽

Interaction Model ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Trait Variation ◽

Genome Wide

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Cross-species alcohol dependence-associated gene networks: Co-analysis of mouse brain gene expression and human genome-wide association data

10.1101/380584 ◽

2018 ◽

Author(s):

Kristin M. Mignogna ◽

Silviu A. Bacanu ◽

Brien P. Riley ◽

Aaron R. Wolen ◽

Michael F. Miles

Keyword(s):

Gene Expression ◽

Alcohol Dependence ◽

Mouse Brain ◽

Gene Networks ◽

Association Studies ◽

Complex Trait ◽

Genome Wide Association ◽

Model Organisms ◽

Genome Wide Association Studies ◽

Genome Wide

AbstractGenome-wide association studies on alcohol dependence, by themselves, have yet to account for the estimated heritability of the disorder and provide incomplete mechanistic understanding of this complex trait. Integrating brain ethanol-responsive gene expression networks from model organisms with human genetic data on alcohol dependence could aid in identifying dependence-associated genes and functional networks in which they are involved. This study used a modification of the Edge-Weighted Dense Module Searching for genome-wide association studies (EW-dmGWAS) approach to co-analyze whole-genome gene expression data from ethanol-exposed mouse brain tissue, human protein-protein interaction databases and alcohol dependence-related genome-wide association studies. Results revealed novel ethanol-regulated and alcohol dependence-associated gene networks in prefrontal cortex, nucleus accumbens, and ventral tegmental area. Three of these networks were overrepresented with genome-wide association signals from an independent dataset. These networks were significantly overrepresented for gene ontology categories involving several mechanisms, including actin filament-based activity, transcript regulation, Wnt and Syndecan-mediated signaling, and ubiquitination. Together, these studies provide novel insight for brain mechanisms contributing to alcohol dependence.

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Proteomics as a Potential Tool for Identifying Biomarkers for Host Resistance to Cattle Tick

Proceedings ◽

10.3390/proceedings2019036131 ◽

2020 ◽

Vol 36 (1) ◽

pp. 131

Author(s):

Ali Raza ◽

Peter James ◽

Ala Tabor

Keyword(s):

Gene Expression ◽

Host Resistance ◽

Serum Proteins ◽

Expression Profiles ◽

Association Studies ◽

Gene Expression Profiles ◽

Economic Losses ◽

Effective Vaccine ◽

Cattle Tick ◽

Genome Wide Association Studies

The cattle tick, Rhiphicephalus microplus, and the diseases it transmits lead to massive economic losses to cattle industries in tropical and subtropical countries. The emergence of widespread resistance to acaricide drugs and the absence of an effective vaccine for tick control had led to genetic selection of host resistance as a method of choice for non-chemical control of cattle tick. Research to identify host genetic markers associated with tick susceptibility or resistance has been limited to the comparison of local breeds in specific geographic regions. Previous studies have also focused on gene expression profiles, localizing cellular and humoral immune responses, and genome-wide association studies (GWAS) to identify functional genetic variants associated with tick resistance/susceptibility. Given the fact that gene expression results and actual dynamics occurring at the protein level often do not correlate due to post-transcriptional, post-translational and degradation regulation, host proteomics may provide reliable biomarkers to assist in selection to support traditional breeding programs. The present study aims to investigate the variation in protein profiles among tick resistant and susceptible cattle following tick infestation. Preliminary findings suggest that different serum proteins exist between tick resistant and susceptible Santa Gertrudis cattle. This research is supported by Meat & Livestock Australia.

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