The Genotype-Tissue Expression (GTEx) Project

Carithers, Latarsha J.; Moore, Helen M.

doi:10.1089/bio.2015.29031.hmm

Cited by 464 publications

(440 citation statements)

References 16 publications

(12 reference statements)

Supporting

Mentioning

435

Contrasting

Unclassified

Order By: Relevance

“…f), indicating that they might not express in normal colorectal tissues because very low measurement values from RNA‐Seq and microarray technologies might be random noise signals . In addition, the two genes were found to be not expressed in the 345 normal colorectal tissues documented in the Genotype‐Expression Project (GTEx) data (with a cut‐off of 1.0 FPKM) . In contrast, the two genes were averagely ranked above 30% of all the measured genes in the 2233 CRC tissues.…”

Section: Resultsmentioning

confidence: 96%

Identification of genes with universally upregulated or downregulated expressions in colorectal cancer

Song

Liu

et al. 2018

J of Gastro and Hepatol

View full text Add to dashboard Cite

Background and Aim Differentially expressed (DE) genes detected at the population‐level through case–control comparison provide no information on the dysregulation frequencies of DE genes in a cancer. In this work, we aimed to identify the genes with universally upregulated or downregulated expressions in colorectal cancer (CRC). Methods We firstly clarified that DE genes in an individual cancer tissue should be the disease‐relevant genes, which are dysregulated in the cancer tissue in comparison with its own previously normal state. Then, we identified DE genes at the individual level for 2233 CRC samples collected from multiple data sources using the RankComp algorithm. Results We found 26 genes that were upregulated or downregulated in almost all the 2233 CRC samples and validated the results using 124 CRC tissues with paired adjacent normal tissues. Especially, we found that two genes (AJUBA and EGFL6), upregulated universally in CRC tissues, were extremely lowly expressed in normal colorectal tissues, which were considered to be oncogenes in CRC oncogenesis and development. Oppositely, we found that one gene (LPAR1), downregulated universally in CRC tissues, was silenced in CRC tissues but highly expressed in normal colorectal tissues, which were considered to be tumor suppressor genes in CRC. Functional evidences revealed that these three genes may induce CRC through deregulating pathways for ribosome biogenesis, cell proliferation, and cell cycle. Conclusions In conclusion, the individual‐level DE genes analysis can help us find genes dysregulated universally in CRC tissues, which may be important diagnostic biomarkers and therapy targets.

show abstract

Section: Resultsmentioning

confidence: 96%

Identification of genes with universally upregulated or downregulated expressions in colorectal cancer

Song

Liu

et al. 2018

J of Gastro and Hepatol

View full text Add to dashboard Cite

show abstract

“…Data from the GTEx consortium (24) and the blood eQTL browser (25) suggested that this was the case for 306 of the 348 CpG-trait associations. 2SMR was used to evaluate the relationship between DNA methylation and gene expression at each of these loci, i.e.…”

Section: Resultsmentioning

confidence: 99%

Systematic Mendelian randomization framework elucidates hundreds of CpG sites which may mediate the influence of genetic variants on disease

Richardson

Haycock

Zheng

et al. 2018

Human Molecular Genetics

View full text Add to dashboard Cite

We have undertaken a systematic Mendelian randomization (MR) study using methylation quantitative trait loci (meQTL) as genetic instruments to assess the relationship between genetic variation, DNA methylation and 139 complex traits. Using two-sample MR, we identified 1148 associations across 61 traits where genetic variants were associated with both proximal DNA methylation (i.e. cis-meQTL) and complex trait variation (P < 1.39 × 10−08). Joint likelihood mapping provided evidence that the genetic variant which influenced DNA methylation levels for 348 of these associations across 47 traits was also responsible for variation in complex traits. These associations showed a high rate of replication in the BIOS QTL and UK Biobank datasets for 14 selected traits, as 101 of the attempted 128 associations survived multiple testing corrections (P < 3.91 × 10−04). Integrating expression quantitative trait loci (eQTL) data suggested that genetic variants responsible for 306 of the 348 refined meQTL associations also influence gene expression, which indicates a coordinated system of effects that are consistent with causality. CpG sites were enriched for histone mark peaks in tissue types relevant to their associated trait and implicated genes were enriched across relevant biological pathways. Though we are unable to distinguish mediation from horizontal pleiotropy in these analyses, our findings should prove valuable in prioritizing candidate loci where DNA methylation may influence traits and help develop mechanistic insight into the aetiology of complex disease.

show abstract

“…4a red, blue, and green regions, respectively). To investigate whether the GWAS-identified SNPs are associated with altered gene expression, which might functionally impact the integrity of these sub-networks, we examined the variants by gene-level cis expression quantitative trait loci (eQTLs) analysis and determined the directional effect of risk alleles using the Genotype-Tissue Expression (GTEx) database (http://www.gtexportal.org) (Carithers and Moore 2015) (see “Methods”). We divided the genes involved in the ‘apoptosis’ cluster into ‘tumor suppressors’ and ‘tumor promoters’ based on their known pro- or anti-apoptotic effects, respectively.…”

Section: Resultsmentioning

confidence: 99%

Network analysis of mitonuclear GWAS reveals functional networks and tissue expression profiles of disease-associated genes

et al. 2016

View full text Add to dashboard Cite

While mitochondria have been linked to many human diseases through genetic association and functional studies, the precise role of mitochondria in specific pathologies, such as cardiovascular, neurodegenerative, and metabolic diseases, is often unclear. Here, we take advantage of the catalog of human genome-wide associations, whole-genome tissue expression and expression quantitative trait loci datasets, and annotated mitochondrial proteome databases to examine the role of common genetic variation in mitonuclear genes in human disease. Through pathway-based analysis we identified distinct functional pathways and tissue expression profiles associated with each of the major human diseases. Among our most striking findings, we observe that mitonuclear genes associated with cancer are broadly expressed among human tissues and largely represent one functional process, intrinsic apoptosis, while mitonuclear genes associated with other diseases, such as neurodegenerative and metabolic diseases, show tissue-specific expression profiles and are associated with unique functional pathways. These results provide new insight into human diseases using unbiased genome-wide approaches.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-016-1736-9) contains supplementary material, which is available to authorized users.

show abstract

The Genotype-Tissue Expression (GTEx) Project

Cited by 464 publications

References 16 publications

Identification of genes with universally upregulated or downregulated expressions in colorectal cancer

Identification of genes with universally upregulated or downregulated expressions in colorectal cancer

Systematic Mendelian randomization framework elucidates hundreds of CpG sites which may mediate the influence of genetic variants on disease

Network analysis of mitonuclear GWAS reveals functional networks and tissue expression profiles of disease-associated genes

Contact Info

Product

Resources

About