Understanding the Functional Contributions and Mechanisms of Type 2 Diabetes Disease-associated Variants (UM1 Clinical Trial Not Allowed)

This Funding Opportunity Announcement (FOA) encourages applications from integrative teams and individual investigators for large-scale complex multi-disciplinary Functional Genomics Projects (FGPs) to determine the contributions and mechanisms underlying the contribution of risk-associated variants and their downstream effector transcripts for type 2 diabetes (T2D). The intent is to generate knowledge and tools to enable the identification of putative biomarkers and therapeutic targets by future efforts. Genome-wide association studies (GWAS) and other genomic studies of T2D and its complications have found many variants that are statistically associated with disease risk, disease protection, progression to complications, or other traits. However, such studies do not show which variants in genomic elements cause these effects or how they result in differences in function. Applications submitted to this RFA will systematically identify causal variants and effector transcripts associated with all known T2D risk variants, verify the role of downstream effector transcripts, build network models that explain their role(s) in T2D and its complications, and identify key readouts and modulation points in these networks. Data, tools, and reagents generated by these projects will be released rapidly to facilitate more in-depth study by the broad scientific community. Awardees to this solicitation will form a Consortium with the Accelerating Medicines Partnership in Type 2 Diabetes Knowledge Portal awardee (AMP T2D KP; RFA-DK-19-505) to accomplish collective goals.