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https://hdl.handle.net/2440/94294
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Type: | Journal article |
Title: | New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk |
Author: | Dupuis, J. Palmer, L. |
Citation: | Nature Genetics, 2010; 42(2):105-116 |
Publisher: | Nature Publishing Group |
Issue Date: | 2010 |
ISSN: | 1061-4036 1546-1718 |
Statement of Responsibility: | Josée Dupuis ... Lyle J Palmer ... et al. |
Abstract: | 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. |
Keywords: | DIAGRAM Consortium GIANT Consortium Global BPgen Consortium Anders Hamsten on behalf of Procardis Consortium MAGIC investigators Humans Diabetes Mellitus, Type 2 Genetic Predisposition to Disease Blood Glucose Fasting Reproducibility of Results Gene Expression Regulation Homeostasis Quantitative Trait, Heritable Polymorphism, Single Nucleotide Alleles Quantitative Trait Loci Databases, Genetic Adolescent Adult Child Meta-Analysis as Topic Genome-Wide Association Study Genetic Loci DNA Copy Number Variations Delta-5 Fatty Acid Desaturase |
Rights: | © 2010 Nature America, Inc. All rights reserved. |
DOI: | 10.1038/ng.520 |
Published version: | http://dx.doi.org/10.1038/ng.520 |
Appears in Collections: | Aurora harvest 7 Translational Health Science publications |
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