Workshop: Beyond genetic associations: using the Association to Function Knowledge Portal to prioritize potential effector genes for complex diseases

Description

Genome-wide association studies (GWAS) have now identified thousands of associated loci for complex diseases and related traits. But despite this success, in only a handful of cases so far have association data been translated to knowledge of causal variants, effector transcripts, biological networks, and potential therapeutic targets. Accelerating progress in this area requires 1) the large-scale integration of genetic association data with detailed, cell type-specific annotation of the epigenome, transcriptome, and proteome, and 2) open-access resources that make these integrated results easily interpretable for research scientists worldwide. 

In this workshop we will present one such resource, the Association to Function Knowledge Portal (A2FKP). Supported by NHGRI as a Genomic Community Resource, the A2FKP integrates high quality genetic and genomic datasets, bioinformatic method results, and expert-curated knowledge for multiple classes of disease, including metabolic, cardiovascular, immunological, pulmonary, musculoskeletal, and neurodegenerative disorders. The A2FKP is being developed in collaboration with the research communities in each of these disease areas. Epigenomic and functional results in the A2FKP are aggregated in collaboration with a sister resource, the Common Metabolic Diseases Genome Atlas (CMDGA). 

Attendees of this workshop will get an overview of the data underlying the A2FKP, will learn how to query the A2FKP both via the web interface and programmatically, and will practice using its interactive tools to form and test hypotheses about loci and genes of interest. Hands-on exercises will provide instruction in using the A2FKP to answer questions such as:

• Do current genetic and genomic data support the involvement of my favorite gene in a particular disease or trait?
• Which gene in a genetically associated locus is most likely to be causal for the associated trait?
• What is the overall genetic architecture of a particular complex disease? 
• For a variant of interest, what is the range of phenotypes with which it is associated? Does it lie within a region that has a potential tissue-specific regulatory role?
• How can I programmatically access the results in the A2FKP?

Attendees are also welcome to bring specific questions from their own research.