Despite much progress in mapping genetic associations for T2D, its complications, and related traits, the underlying causal variants, effector genes, and gene networks are not well understood. The AMP-T2D consortium aims to accelerate the pace by which these disease mechanisms are elucidated, through generation and integration of novel genomic data interrogating genetic associations. This project addresses RFA-DK-19-505 ?Limited Competition for the Accelerating Medicines Partnership (AMP) in Type 2 Diabetes Knowledge Portal (UM1)? and will be conducted by the leaders of the current AMP T2D Knowledge Portal (T2DKP). Its goal is to continue development of the T2DKP by enhancing its infrastructure to aggregate, analyze, and visualize genetic and genomic datasets and results, thereby helping to identify causal risk variants and effector genes for T2D and its complications. The goal of specific aim 1 is to enhance the data and knowledge base for the T2DKP. It will enhance the T2DKP software platform to represent additional classes of ?omic and phenotypic data, integrate datasets relevant to AMP-T2D within a federated data warehouse, develop new methods and analytical pipelines to analyze these data, and enable them to be accessed by download or application programming interfaces (APIs). The goal of specific aim 2 is to enhance the publicly accessible T2DKP web interface. It will develop new web modules to visualize datasets within the T2DKP, extend the T2DKP with tools from external public genomic databases, maintain curated knowledge lists for T2D and its complications, allow users to customize data and tools shown within the T2DKP, and update the T2DKP in response to stakeholder feedback. The goal of specific aim 3 is to coordinate the AMP-T2D consortium. It will provide operational support for AMP-T2D investigators, foster collaborations with external partners, track and ensure the timely release of AMP-T2D datasets, administer an opportunity pool to fund additional AMP-T2D projects, and conduct outreach and training on the T2DKP. Significance: The project would extend the T2DKP with new capabilities to integrate and display datasets with information regarding causal variants, effector transcripts, and gene networks for T2D and its complications. Public access to these data and results will significantly accelerate efforts to identify new therapeutic strategies to prevent, treat, or reverse T2D and its complications.

Public Health Relevance

The AMP-T2D consortium aims to accelerate the pace by which type 2 diabetes (T2D) disease mechanisms are elucidated, through generation and integration of novel genomic datasets. This project will continue to develop the AMP-T2D Knowledge Portal (T2DKP), a public resource of genomic datasets relevant to T2D, its complications, and related traits. Extending this resource will enable AMP-T2D investigators, as well as researchers worldwide, to more easily share genomic datasets and use them to interrogate T2D disease mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
2UM1DK105554-06
Application #
10064798
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Zaghloul, Norann
Project Start
2015-05-01
Project End
2025-06-30
Budget Start
2020-08-20
Budget End
2021-06-30
Support Year
6
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Broad Institute, Inc.
Department
Type
DUNS #
623544785
City
Cambridge
State
MA
Country
United States
Zip Code
02142