Advertisement

Topics

Opportunities and challenges for transcriptome-wide association studies.

08:00 EDT 1st April 2019 | BioPortfolio

Summary of "Opportunities and challenges for transcriptome-wide association studies."

Transcriptome-wide association studies (TWAS) integrate genome-wide association studies (GWAS) and gene expression datasets to identify gene-trait associations. In this Perspective, we explore properties of TWAS as a potential approach to prioritize causal genes at GWAS loci, by using simulations and case studies of literature-curated candidate causal genes for schizophrenia, low-density-lipoprotein cholesterol and Crohn's disease. We explore risk loci where TWAS accurately prioritizes the likely causal gene as well as loci where TWAS prioritizes multiple genes, some likely to be non-causal, owing to sharing of expression quantitative trait loci (eQTL). TWAS is especially prone to spurious prioritization with expression data from non-trait-related tissues or cell types, owing to substantial cross-cell-type variation in expression levels and eQTL strengths. Nonetheless, TWAS prioritizes candidate causal genes more accurately than simple baselines. We suggest best practices for causal-gene prioritization with TWAS and discuss future opportunities for improvement. Our results showcase the strengths and limitations of using eQTL datasets to determine causal genes at GWAS loci.

Affiliation

Journal Details

This article was published in the following journal.

Name: Nature genetics
ISSN: 1546-1718
Pages: 592-599

Links

DeepDyve research library

PubMed Articles [27787 Associated PubMed Articles listed on BioPortfolio]

Probabilistic fine-mapping of transcriptome-wide association studies.

Transcriptome-wide association studies using predicted expression have identified thousands of genes whose locally regulated expression is associated with complex traits and diseases. In this work, we...

Transcriptome-wide association study identifies new candidate susceptibility genes for glioma.

Genome-wide association studies (GWAS) have so far identified 25 loci associated with glioma risk, with most showing specificity for either glioblastoma (GBM) or non-GBM tumors. The majority of these ...

CASMAP: Detection of statistically significant combinations of SNPs in association mapping.

Combinatorial association mapping aims to assess the statistical association of higher-order interactions between genetic markers with a phenotype of interest. This paper presents CASMAP, a software p...

Pulmonary Function: From Genome Wide Association Studies to Genome-Wide Interaction Studies.

Genome-wide association studies and polygenic risk scores for skin cancer: clinically useful yet?

Genome-wide association studies (GWAS) have identified thousands of susceptibility variants, though most have been associated with small individual risk estimates that offer little predictive value. H...

Clinical Trials [4111 Associated Clinical Trials listed on BioPortfolio]

PheWAS of a Polygenic Predictor of Thyroid Function

Performing a phenome-wide association study (PheWAS) identifying clinical diagnoses associated with a polygenic predictor of Thyroid stimulating hormone (TSH) levels identified by a previo...

The Mechanism and Prognosis of Pulmonary Circulation Dysfunction

Venous thromboembolism (VTE) is a condition which influenced by both environmental and genetic factors. This study is going to explore new significant Single nucleotide polymorphisms (SNPs...

Genome-Wide Association Study in Patients With Nontuberculous Mycobacterial Lung Disease

The aim of this study was to elucidate genetic susceptibility of patients with nontuberculous mycobacterial lung disease using genome-wide association study.

Cultural Congruence in International Genetics Research

This study will explore how cultural differences influence genetics research in developing countries. Human genetics research is becoming more common in developing countries. However, when...

Transcriptome Assessment After Cardiac Arrest

The purpose of this study is to determine whether the blood transcriptome of patients resuscitated after out-of-hospital could be an early predictor of the neurological outcome.

Medical and Biotech [MESH] Definitions

Gap between individuals, households, businesses and geographic areas at different socioeconomic levels with regard to both their opportunities to access electronic information and communication technologies (ICTs). Their use of the Internet for a wide variety of activities, reflects various differences among and within countries.

Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are CASE-CONTROL STUDIES; COHORT STUDIES; and CROSS-SECTIONAL STUDIES.

Works about research studies that evaluate interventions or exposures on biomedical or health-related outcomes. The two main types of clinical studies are interventional studies (clinical trials) and observational studies.

An application that must be submitted to a regulatory agency (the FDA in the United States) before a drug can be studied in humans. This application includes results of previous experiments; how, where, and by whom the new studies will be conducted; the chemical structure of the compound; how it is thought to work in the body; any toxic effects found in animal studies; and how the compound is manufactured. (From the "New Medicines in Development" Series produced by the Pharmaceutical Manufacturers Association and published irregularly.)

The non-genetic biological changes of an organism in response to challenges in its ENVIRONMENT.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Gene Expression
The process of gene expression is used by eukaryotes, prokaryotes, and viruses to generate the macromolecular machinery for life. Steps in the gene expression process may be modulated, including the transcription, RNA splicing, translation, and post-tran...

Psychiatry
Psychiatry is the study of mental disorders and their diagnosis, management and prevention.  Conditions include schizophrenia, severe depression and panic disorders among others. There are pharmaceutical treatments as well as other therapies to help...


Searches Linking to this Article