GWAS Diagram Browser

This section aims to provide some guidance on how to use the new dynamic GWAS diagram. For an introduction to the GWAS catalog, see the "About" tab.

How to ...

• Zoom: There are two ways in which the diagram can be zoomed. The easiest option is to use the scroll wheel on the mouse or touch pad on a laptop. Scrolling up zooms in and scrolling down zooms out. This feature may not work with all touch pads. Alternatively, the left-hand side of the diagram features a zoom bar which can be used to generate exactly the same effect, by dragging the little square up or down the bar with the mouse pointer. The diagram currently zooms from the top left corner, so even if you zoom using a mouse scroll wheel, you may have to move the diagram to get to the desired area. The zoom bar occasionally appears in the wrong place. This is a known bug. Refreshing the browser window usually solves the problem.
• Move the diagram: The diagram can be moved around the viewing area by clicking on any part of the diagram with the left mouse button and, holding the mouse button down, dragging the diagram around the screen until the desired part is visible. This feature is particularly useful for centering the diagram on a specific location at higher zoom levels.
• Display the legend: A legend of the colour scheme is available in the "Legend" box in the top right corner of the diagram. Simply click on the box to expand ("Show legend") or hide ("Hide legend") the legend. Click on any link in the legend to filter the diagram by that category. This does not work for any of the "other"-type categories (other measurement, other disease and other trait).
• Display labels: Chromosomes and traits (coloured circles) have labels that display when hovering the mouse pointer over a given element. The displayed labels correspond to the EFO term mapped this SNP.
• Display SNP information: To view all the SNPs associated with any trait in a given location, simply click on the trait you are interested in. An interactive pop-up will display the SNPs for that trait, the p-value for each SNP-trait association, the study in which the association was identified and the EFO term the SNP-trait association is mapped to. The SNP, EFO term and study fields are interactive, linking out to Ensembl, EFO and UKPMC, respectively. There is also a link to the entry for this SNP in the GWAS catalog. The pop-up can be moved around the screen. Clicking on another trait automatically closes the current pop-up. Alternatively, close the pop-up by clicking on the cross in its top right corner.
• Filter the diagram: The full diagram can be filtered by typing a trait into the text box above the diagram and hitting "Enter" or clicking the "Query" button.
  • If the trait is available in the diagram, all other traits will be faded to a lower visibility to highlight the desired trait.
  • Searchable traits are based on EFO categories and may not coincide with curator-assigned trait names, e.g. a search for "hair color" will highlight SNP-trait associations labelled hair color as well as "black vs blond hair" and "red vs non-red hair".
  • The text box has auto-complete functionality based on EFO. The auto-complete may take a moment to start loading. Only a limited number of terms can be displayed at a time, so if your term does not appear immediately, carry on typing. Due to the structure of the ontology, the presence of a term in the auto-complete does not guarantee that there are any corresponding traits in the diagram!
  • More advanced filtering capabilities, such as p-value and time, are under development, so check back regularly for updates.

Diagram features

• Colours: A new colour scheme for the GWAS diagram has been developed in collaboration with the catalogue curators. The legend is available for viewing in the top right corner of the diagram. It can also be downloaded as a PNG file from the "Downloads" tab. For more details on the colour categories, see below.
• Time series: A slide show of consecutive GWAS diagrams from 2005 to present is available in the "Time series views" tab. The time interval between each diagram is six months, including all dates up to the end of either June or December of that year. The slide show auto-advances at a pace of 2 seconds per slide. It can be paused, started and navigated by moving the cursor into the diagram area, which brings up a set of navigation button in the top left corner.
• Trait-specific views: A slide show of GWAS diagrams for common traits is available in the "Trait-specific views" tab. The slide show auto-advances at a pace of 2 seconds per slide. It can be paused, started and navigated by moving the cursor into the diagram area, which brings up a set of navigation button in the top left corner.
• Downloads: All time series and trait-specific images are available for download as png files in the "Downloads" tab. Various ontology files are also available, including Experimental Factor Ontology and the GWAS schema ontology and knowledge base.

Colour categories

A new colour scheme for the GWAS diagram has been developed in collaboration with the catalogue curators. The selection of the different colour categories is data-driven; categories used in more than 150 individual SNP-trait associations were given their own colour, while less used categories were aggregated into broader categories such as "Other disease". Categories are EFO classes and a category is "used" if it or any of its subclasses has been mapped to a GWAS trait and this trait is in turn part of a SNP-trait association. To see which subclasses belong to any category, click on that category in the legend to proceed to a view of the EFO tree in Bioportal. Below is a list of examples of the kind of traits that belong to each category. Some traits may belong to multiple categories.

• Digestive system disease: any disease that affects a part of the digestive system, such as celiac disease or pancreatitis
• Cardiovascular disease: any disease of the cardiovascular system, such as aortic aneurysm or coronary heart disease.
• Metabolic disease: any disorder caused by an abnormal metabolic process, such as type II diabetes, metabolic syndrome or vitamin D deficiency
• Immune system disease: any disease of the immune system, such lupus erythematosus, psoriasis or sarcoidosis
• Nervous system disease: any disease of the nervous system, including Alzheimer's disease or autism
• Liver enzyme measurement: any quantification of liver enzymes, typically in blood, such as alanine transaminase measurement or gamma glutamyl transpeptidase measurement
• Lipid or lipoprotein measurement: any quantification of some circulating lipid or some lipoprotein in all or part of the body, such as LDL cholesterol measurement
• Inflammatory marker measurement: any measurement of a protein with a known inflammatory response, e.g. C-reactive protein measurement or interleukin 10 measurement
• Hematological measurement: a measurement quantifying some blood cell or component, including hematocrit and platelet count
• Body weights and measures: this category includes measurements of height, weight, area etc of the human body and its parts, such as body weight or body mass index.
• Cardiovascular measurements: measurement of some part of the cardiovascular system, e.g. ankle brachial index or QT interval
• Other measurement: any measurement not covered by the preceeding categories, including cortical thickness or fasting blood glucose measurement
• Response to drug: any trait that is the result of a drug stimulus
• Biological process: any activity of a living organism that supports life, e.g. odontogenesis or behaviour
• Cancer: this category includes any kind of tissue growth resulting from uncontrolled cell proliferation, usually, although not necessarily, malignant. Examples include breast cancer and Hodgkins lymphoma
• Other disease: any disease that does not fit into any of the preceeding categories. Examples include genetic disorders and skeletal system diseases.
• Other trait: any trait that does not fit into any of the preceeding categories, e.g. hair color, eye color or brain structure

Questions, requests and bug reports

For questions, feature requests or bug reports, please contact Dani Welter at EBI. In particular, please let us know if a given feature does not behave as described. Always specify in which web browser, including which version, and which operating system the problem occurred. This application is tested in all the latest versions of Mozilla Firefox, Google Chrome, Safari and Internet Explorer. If you find an older browser version which does not work, please let us know. In this event, click here for a static version of the diagram in PNG format.

Background

The National Human Genome Research Institute (NHGRI) Catalog of Published Genome-Wide Association Studies or GWAS catalogue provides a quality controlled, manually curated, literature-derived collection of all published GWA studies assaying at least 100,000 SNPs and all SNP-trait associations with p-values < 1.0 × 10^-5 (Hindorff et al., 2009). The catalogue can be searched by a number of options including journal, first author, trait, chromosomal region, gene, SNP, odds ratio and p-value threshold. As of 20/08/12, it includes 1355 publications and 7226 SNPs. In addition to the SNP-trait association data, the catalogue also publishes the iconic GWAS diagram of all SNP-trait associations, with p-values ≤ 5.0 × 10^-8, mapped to the SNPs’ chromosomal locations. The diagram is released quarterly and the latest version of the diagram is made available on the GWAS catalogue website in PDF format and as a PowerPoint slide.

The GWAS diagram browser

This page hosts a novel system that generates the GWAS diagram dynamically using semantic web technologies. The diagram produced in this fashion can be filtered and searched at different levels of granularity and by different criteria, currently including trait (main diagram tab) and publication date (time series tab, currently availabe for a fixed set of time points only). It is possible to zoom in over chromosomes in order to see all SNP-trait associations for a given region. SNP-trait associations are shortly going to be fully interactive. Trait name information is already available on mouse-over and traits being clickable to allow proceeding from an association to the catalogue entry and to the publication is currently under development.

The diagram is generated in SVG (Scalable Vector Graphics) as a web application with a Java back-end using an Apache Tomcat server. The catalogue data is presented as a knowledge base, based on the GWAS Catalog schema ontology, which formalises the relationship between various concepts such as SNP, trait and study. Both the knowledge base and the schema ontology can be found in the "Downloads" tab. The traits in the GWAS catalog are formalised by mapping each trait to one or more terms in the Experimental Factor Ontology (EFO). Mapping traits to an ontology provides querying capabilities across multiple traits and trait categories. In the case of cancer for example, a single query can identify all traits related to cancer whereas in the GWAS catalog, such a query would require each cancer-related trait to be selected manually. The EFO-driven SNP-trait associations also form the basis of the new colour scheme of the dynamic GWAS diagram.

Contact

For questions and to provide feedback, please contact Dani Welter at EBI.

For bug reports and feature requests, please use our bug tracker.

Hindorff, L.A., Sethupathy, P., Junkins, H.A., Ramos, E.M., Mehta, J.P., Collins, F.S. and Manolio, T.A. (2009) Potential Etiologic and Functional Implications of Genome-Wide Association Loci of Human Diseases and Traits. Proc. Natl. Acad. Sci. USA. 106, 9362–9367.