Blog

In recent years, the increase in availability of DNA methylation measures in population-based cohorts and case-control studies has resulted in a dramatic expansion of the number of epigenome-wide association studies (EWAS). 

In this conversation with Thomas Battram, Senior Research Associate in Molecular Epidemiology at University of Bristol, we dig deeper into the EWAS Catalog, a rich and accessible database of epigenome-wide association studies explored in his recent Software Tool Article on Wellcome Open Research. We discuss the scope and importance of the field of epigenetics as well as the strengths, innovations, and implications of the Catalog.   

The field of epigenetics 

Fundamentals of genetics  

Sequences of DNA base pairs – adenine (A), cytosine (C), guanine (G), thymine (T) – often operate as functional units called genes. Genes serve as the coded instructions for producing specific molecules, such as proteins. The full DNA sequence or genome of a human is pretty much the same in all cells of its body. However, the gene’s role and its products may have very different functions in different cell types, for example, brain cells compared to blood cells.  

Epigenetic marks  

Epigenetic marks play a role in determining the type and amount of gene product expressed so that the same gene can have very different impacts across cells and time. In fact, epigenetic marks are largely responsible for determining and maintaining cell type identity. In addition to differences between cell types, epigenetic marks are known to differ in the same cell types between individuals, vary in response to some exogenous environmental exposures, and are correlated with disease risk.  

Most disease-correlated epigenetic marks do not actually cause disease. These vary due to the presence of disease or due to processes influencing disease risk. In some cases, marks may play a role in disease risk. Consequently, these marks may be targeted to prevent or in rare cases reverse disease. Correlated marks that do not play a role in disease risk may be useful for the early detection of disease (for example, some cancers) or to identify high-risk individuals who could benefit from an intervention.  

DNA methylation and epigenome-wide association studies (EWAS) 

DNA methylation is the most investigated epigenetic mark. This is because DNA collection and DNA methylation measurement and interpretation are easy to conduct. 

DNA methylation marks are present at around 30 million locations in the human genome. The most common and cost-effective platform for measuring DNA methylation only accounts for 850,000 of these locations.  

Analyzing DNA methylation measurements to assess how it relates to exposures and traits is called an epigenome-wide association study (EWAS). In the past decade, researchers have performed and published thousands of EWAS. 

The EWAS Catalog 

A database of EWAS associations 

The EWAS Catalog is a database containing associations from published EWAS. An EWAS association is simply a quantifiable measure of how DNA methylation changes relate to differences in a trait between individuals. The stronger the magnitude of the association, the stronger the relationship between DNA methylation and the trait.   

There are currently 2,059,897 associations from 6,996 EWAS within the database. We have made this wealth of data easily searchable via a website where researchers can look up exposures, traits, regions of the genome, or studies of interest. Alternatively, the full database can all be downloaded directly.   

Differences with other databases 

Most other databases focus on specific traits or diseases. The EWAS Catalog does not restrict to specific traits. It’s the only database that includes full statistics from hundreds of EWAS performed in the Avon Longitudinal Study of Parents and Children for a comprehensive selection of exposures and traits. This addition fills gaps in the existing published EWAS literature. Furthermore, The EWAS Catalog team provides a simple way for users to upload their own data. 

Implications  

Potential impact 

The EWAS Catalog can serve as a valuable tool for researchers. In the past, scholars have interpreted the genomic regions in their studies based on the functions of nearby genes. Our Catalog allows for a systematic comparison of such regions to all published EWAS. As a result, we believe it can help gain a deeper understanding of the relationship between DNA methylation changes and human traits. 

Next steps  

The team will continue to extract and input EWAS data into the database. We also plan to provide additional tools to help researchers examine and compare their own EWAS to all published studies. Such steps could further improve the understanding of their EWAS results. 

Choosing Wellcome Open Research as a publishing venue  

Publishing with Wellcome Open Research has been far easier compared to other publishers. The team was very responsive after submission and their instructions were also very clear. 

 In addition, having all reviewer comments and author replies openly available is brilliant. I hope more publishers will follow a similar route in the future. 

You can read the full Software Tool Article and its peer review reports on Wellcome Open Research: ‘The EWAS Catalog: a database of epigenome-wide association studies’ >>