Project: AMP-T2D

AMP-T2D

The Accelerating Medicines Partnership in Type 2 Diabetes is a consortium of government, academic and industry scientists advancing genomic discovery in T2D with a view to therapeutic development. Its central mandate is to construct a Type 2 Diabetes Knowledge Portal where genomic and metagenomic information on T2D and related phenotypes is assembled, curated, and deposited …

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DPP

The Diabetes Prevention Program randomized participants at high risk of T2D (based on impaired glucose tolerance, an elevated fasting glucose and overweight) to placebo, metformin, or intensive lifestyle modification. Both the metformin and lifestyle interventions proved effective in preventing or delaying the onset of diabetes [DPP NEJM paper], and these effects were sustained [DPP Lancet …

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GENIE/JDRF DNCRI

The GEnetics of Nephropathy – an International Effort consortium assembles investigators at the Massachusetts General Hospital, Boston Children’s Hospital and Broad Institute in Boston, the University of Helsinki, Queen’s University Belfast, University College Dublin, the University of Michigan and the University of Pennsylvania to discover genetic determinants of diabetic kidney disease (D). It catalyzed the formation …

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IGF2

A variant that disrupts an intron-exon splice junction in IGF2 protects from T2D in Mexican populations [Mercader Diabetes paper]. …

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Insulin secretion assay

Sean Burns and colleagues developed a high-throughput insulin secretion assay that can measure real-time insulin secretion in beta cells [Burns Cell Metabolism paper]. This system can be used for functional characterization of associated genetic loci (e.g. mutated via CRISPR/Cas9 approaches) and screening of small molecules for an impact on insulin secretion. …

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MAGIC

The Meta-Analyses of Glucose and Insulin-related traits Consortium was formed to identify the genetic determinants of quantitative glycemic traits in non-diabetic individuals. It has discovered multiple loci influencing fasting and dynamic masures of glycemia, insulin secretion and insulin action, as described in the publications section. In doing so, it has provided a rich dataset in …

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MetGen

An NIH-convened workshop [Pawlyk Diabetes paper] led to the formation of the Metformin Genetics Consortium, led by groups at the University of Dundee (Ewan Pearson, PI), the University of California in San Francisco (Kathy Giacomini, PI) and MGH/Broad (Jose Florez, PI). It seeks to assemble a large collection of samples where the pharmacogenetics of metformin …

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PHARMGen

The Patients with Hyperglycemia Assessed for Response to Medications by Genetics study is a retrospective clinical cohort of several thousand participants with T2D culled from electronic medical record databases where prescription information and glycemic response is available. Volunteers provide a DNA sample and pharmacogenetic assessments of drug response in a real world setting can be …

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SIGMA

The Slim Initative for Genomic Medicine in the Americas is a partnership between the Fundación Carlos Slim the Broad Institute and Mexican collaborators to advance research on key diseases of relevance in Latin America, such as cancer, type 2 diabetes, and kidney disease. The type 2 diabetes component has made the following fundamental discoveries: Association …

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SIGMA MMTT

The SIGMA mixed-meal tolerance test study challenges non-diabetic participants with a high-calorie, high-carbohydrate meal reflective of current US dietary patterns, before and after a short course of metformin. Their glycemic, hormonal and metabolomic responses to the dietary and pharmacological perturbations can be studied according to genotype at selected loci. …

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SLC16A11

The T2D-associated gene SLC16A11 increases risk of T2D by ~30% in Latino populations. It encodes a monocarboxylate transporter. Members of the Florez group have characterized its transport function, verified that non-coding variants in the T2D risk haplotype reduce expression of SLC16A11 in hepatocytes, coding variants in the same haplotype impair its interaction with the chaperone …

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SUGAR-MGH

The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans is a pharmacogenetic resource in which 1,000 volunteers who were naïve to T2D medications received a glipizide challenge and a short course of metformin, after which they underwent an oral glucose tolerance test (OGTT). Their glycemic, hormonal and metabolomic …

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T2D-GENES

The Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples consortium assembled 10,000 samples from T2D cases and controls from five ethnic groups (European, African, Latino, South Asian and East Asian descent) and conducted whole-exome sequencing to identify rare coding variants associated with type 2 diabetes. In addition, 600 Hispanic members of extended …

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