NIDDK is soliciting applications to this RFA and its companion RFA (RFA-DK-19-505) to address the overarching goals of 1) accelerating the pace of understanding of the genetic architecture of T2D and its complications, 2) identifying effector transcripts with predicted causal relationship to T2D and its complications, 3) validating the strength of predicted effector transcripts through experimental work and their placement in networks, and 4) making this information broadly available to the scientific community to foster fundamental and clinical research ultimately resulting in the identification of potential biomarkers for disease and the discovery of potential therapeutic targets. To accomplish these goals awardees to the AMP T2D KP (RFA-DK-19-505) and Functional Genomic Projects (FGPs; RFA-DK-19-012) will continue the AMP T2D Consortium, working together toward the overarching goals.
Type 2 diabetes (T2D) currently affects over 300 million people worldwide and its prevalence is increasing rapidly. T2D is characterized by insulin resistance, beta cell failure, dysregulated insulin secretion by pancreatic beta-cells, and additional metabolic disturbances. Dysglycemia along with other metabolic disturbances of T2D lead to significant complications due to end organ damage. Although the current rise in prevalence is driven by environmental factors such as life-style, it is now appreciated that complex genetic determinants contribute to an inherent susceptibility to T2D and its complications. Common and rare variant genome-wide studies and exome sequencing have yielded greater than 400 loci that have significant associations with T2D, related metabolic traits, and/or diabetic complications. For the purposes of this RFA, the terms “disease” and “trait” are used broadly, to encompass diseases, risk of diseases, protective effects against diseases, complications, molecular phenotypes, organismal phenotypes, clinical phenotypes or outcomes, responses to therapeutic drugs, and other outcomes relevant to human health and disease.
Translation of many of these disease-associated risk loci to causal variants and their downstream effector transcripts (coding or non-coding) has been complicated by the fact that the risk loci often lie in non-coding regions of the genome, far from the effector transcript they regulate. Through work accomplished by the AMP T2D Consortium, an unprecedented amount of human genomic and epigenomic data around T2D have been collated and analyzed, leading to the initial identification of over 130 possible effector transcripts . While many probable effector transcripts have been identified, in many cases their causal role has not yet been validated nor their, mechanism of action determined, and their full impact on traits has not been elucidated. At the same time, there remain significant amounts of genomic information around T2D and its complications that can be added to the AMP T2D KP as well as additional ‘omics and other data types that can be incorporated or integrated into its existing foundation.
Filed Under: Funding Opportunities