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

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dc.contributor.authorDupuis, J.
dc.contributor.authorPalmer, L.
dc.date.issued2010
dc.description.abstractLevels 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.
dc.description.statementofresponsibilityJosée Dupuis ... Lyle J Palmer ... et al.
dc.identifier.citationNature Genetics, 2010; 42(2):105-116
dc.identifier.doi10.1038/ng.520
dc.identifier.issn1061-4036
dc.identifier.issn1546-1718
dc.identifier.orcidPalmer, L. [0000-0002-1628-3055]
dc.identifier.urihttp://hdl.handle.net/2440/94294
dc.language.isoen
dc.publisherNature Publishing Group
dc.rights© 2010 Nature America, Inc. All rights reserved.
dc.source.urihttps://doi.org/10.1038/ng.520
dc.subjectDIAGRAM Consortium
dc.subjectGIANT Consortium
dc.subjectGlobal BPgen Consortium
dc.subjectAnders Hamsten on behalf of Procardis Consortium
dc.subjectMAGIC investigators
dc.subjectHumans
dc.subjectDiabetes Mellitus, Type 2
dc.subjectGenetic Predisposition to Disease
dc.subjectBlood Glucose
dc.subjectFasting
dc.subjectReproducibility of Results
dc.subjectGene Expression Regulation
dc.subjectHomeostasis
dc.subjectQuantitative Trait, Heritable
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAlleles
dc.subjectQuantitative Trait Loci
dc.subjectDatabases, Genetic
dc.subjectAdolescent
dc.subjectAdult
dc.subjectChild
dc.subjectMeta-Analysis as Topic
dc.subjectGenome-Wide Association Study
dc.subjectGenetic Loci
dc.subjectDNA Copy Number Variations
dc.subjectDelta-5 Fatty Acid Desaturase
dc.titleNew genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
dc.typeJournal article
pubs.publication-statusPublished

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