Accelerating Medicines Partnership in Type 2 Diabetes (AMP T2D) Renewal

May 2019 Council

Lead Division/Office

DEM

Point(s) of Contact

Aaron Pawlyk, Ph.D.

Executive Summary

Type 2 diabetes (T2D) exerts a significant and growing global burden on health and healthcare systems, affecting over 300 million people worldwide and its prevalence is increasing rapidly. It is characterized by insulin resistance, beta cell failure, and dysregulated insulin secretion by pancreatic beta-cells. Although the current rise in T2D prevalence is driven mainly by changes in life-style, complex genetic determinants are widely considered to contribute to an inherent susceptibility to this disease.

Despite many advances in treatment options there are no truly disease modifying therapies for T2D, a paucity of effective treatments for many of its complications, and no reliable predictive risk markers. To address this lack, The Accelerating Medicines Partnership (AMP) was established as a pre-competitive collaboration among government, academia, and industry to aggregate and mine human genetic data to identify novel therapeutic target and biomarker candidates. To date, the partnership has leveraged existing and newly generated data to identify >400 genomic risk variants and >70 probable target/biomarker effector transcripts and laid the groundwork to identify additional risk variants and effector transcripts.

The overarching goal of AMP T2D is to use human genetics as a powerful approach to obtain human-data derived disease understanding and biomarker/therapeutic opportunities. This is being accomplished through systematic aggregation of existing genotype-phenotype data for T2D, related traits, and its complications as well as the generation of a large amount of new ‘omic data. The goal of the NIDDK-funded component of the consortium is to aid in advancing the understanding of the mechanisms responsible for T2D development through the integration of large-scale genetic data that will contribute to further deconstruction of the pathophysiology of T2D, and potentially of its major complications, including macrovascular and microvascular disease.

The T2D Knowledge Portal (T2D KP) aggregates and harmonizes ‘omics data with associated phenotypic information to identify relationships between sequence variation in potential targets in the genome and risk/protection from T2D, complications, and related intermediate metabolic endpoints. The T2D KP provides automated analytical methods and query tools to provide the clearest and most interpretable answers about the relationships between gene function and diabetes related phenotypes.