Research Domain: Genetic Discovery

TCF7L2 Genetic Variation Augments Incretin Resistance and Influences Response to a Sulfonylurea and Metformin: The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH)

OBJECTIVE The rs7903146 T allele in transcription factor 7 like 2 (TCF7L2) is strongly associated with type 2 diabetes (T2D), but the mechanisms for increased risk remain unclear. We evaluated the physiologic and hormonal effects of TCF7L2 genotype before and after interventions that influence glucose physiology. RESEARCH DESIGN AND METHODS We genotyped rs7903146 in 608 …

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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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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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SIGMA

The Slim Initative for Genomic Medicine in the Americas is a partnership between the Fundaci√≥n 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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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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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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Genetic Discovery

The sequencing of the human genome, the characterization of the patterns of human genetic variation, and technological and methodological advances in genotyping and sequencing studies have underwritten a veritable explosion in genetic discovery. Crucially, these studies have queried the entire human genome in an agnostic fashion, free from the constraints of pre-existing biological knowledge and …

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Genome-wide association study of the modified Stumvoll Insulin Sensitivity Index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci

Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose …

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The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to …

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