New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

By Nature Genetics, Josée Dupuis, C. Langenberg, I. Prokopenko, R. Saxena, N. Soranzo, A. Jackson, Eleanor Wheeler, Nicole L. Glazer, N. Bouatia-Naji and 296 more. Nature Genetics, 2010

2,246 citations recorded by the source corpus.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

Subfields: Endocrinology, Diabetes and Metabolism, Genetics, Surgery

View Paper: https://www.semanticscholar.org/paper/ed1e67bb908e298a27ff5100ea27df35792fd148

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In Endocrinology, Diabetes and Metabolism

1. Cosetta Minelli
2. Nuala Sheehan

In Genetics

1. Cosetta Minelli
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Citations in the corpus

• Beta Cell Dysfunction and Insulin Resistance (2013, neutral): “…architecture of quantitative indices of beta cell function and of insulin resistance differ markedly: given the same individuals, sample sizes, and biochemical measurements, more signals were described for beta cell function compared to insulin resistance (Dupuis et al., 2010; Voight et al., 2010).”
• Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis (2010, neutral): “Overall, these data are consistent with the impression that common T2D risk alleles more often act through beta-cell dysfunction 12 , 44 , but they provide further examples of T2D risk variants that exert their primary effects on insulin action.”
• Fast and Rigorous Computation of Gene and Pathway Scores from SNP-Based Summary Statistics (2016, neutral): “For insulin resistance[34] we found the REACTOME pathway insulin signal attenuation to be genome-wide significant.”
• The Metabochip, a Custom Genotyping Array for Genetic Studies of Metabolic, Cardiovascular, and Anthropometric Traits (2012, neutral): “The Metabochip was designed by representatives of the Body Fat Percentage [9], CARDIoGRAM (coronary artery disease and myocardial infarction) [10], DIAGRAM (type 2 diabetes) [11], GIANT (anthropometric traits) [3,12,13], Global Lipids Genetics (lipids) [4], HaemGen (hematological measures) [14], ICB”