January 28, Cambridge – Researchers at EMBL’s European Bioinformatics Institute (EMBL-EBI) and the Wellcome Sanger Institute have developed a novel approach, called GARFIELD, that can assess the functional consequences of genetic variants associated with specific diseases. Such methods have the potential to drive new biological insights and prioritise variants for further exploration.

GARFIELD is a functional enrichment method that leverages findings from genome-wide association studies (GWAS) and regulatory or functional annotations, in order to classify features relevant to a disease or trait of interest. It accounts for major sources of confounding, incorporates analysis of sub-threshold associations for relatively underpowered GWAS studies and provides the largest number of enrichments on real data among methods with full control of false positive rate in simulated data.

The method, detailed in a paper published in Nature Genetics, was used to analyse the enrichment patterns of publicly available GWAS summary statistics. This uncovered statistically significant enrichments for the majority of traits being considered, and highlighted clear differences in enrichment patterns between traits. The analysis uncovered enrichments that reflected current understanding of key cellular types for disease, and also produced novel observations.

The paper authors also developed software to make GARFIELD more accessible to the research community, including tools for visualising the enrichment results that scale to thousands of potential functional elements.

The standalone GARFIELD tool is available on the EMBL-EBI website and the GARFIELD R-package can be accessed here.

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