New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
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Version: Author's accepted manuscript
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State: Public
Version: Author's accepted manuscript
License: Not specified
Serval ID
serval:BIB_68555FB264D9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
Journal
Nature genetics
Working group(s)
DIAGRAM Consortium, GIANT Consortium, Global BPgen Consortium, Anders Hamsten on behalf of Procardis Consortium, MAGIC investigators
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
02/2010
Peer-reviewed
Oui
Volume
42
Number
2
Pages
105-116
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
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
Adolescent, Adult, Alleles, Blood Glucose/genetics, Blood Glucose/metabolism, Child, DNA Copy Number Variations/genetics, Databases, Genetic, Diabetes Mellitus, Type 2/genetics, Fasting/blood, Gene Expression Regulation, Genetic Loci/genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Homeostasis/genetics, Humans, Meta-Analysis as Topic, Polymorphism, Single Nucleotide/genetics, Quantitative Trait Loci/genetics, Quantitative Trait, Heritable, Reproducibility of Results
Pubmed
Web of science
Create date
25/01/2010 15:38
Last modification date
14/01/2022 7:10