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

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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
Author(s)
Dupuis J., Langenberg C., Prokopenko I., Saxena R., Soranzo N., Jackson A.U., Wheeler E., Glazer N.L., Bouatia-Naji N., Gloyn A.L., Lindgren C.M., Mägi R., Morris A.P., Randall J., Johnson T., Elliott P., Rybin D., Thorleifsson G., Steinthorsdottir V., Henneman P., Grallert H., Dehghan A., Hottenga J.J., Franklin C.S., Navarro P., Song K., Goel A., Perry J.R., Egan J.M., Lajunen T., Grarup N., Sparsø T., Doney A., Voight B.F., Stringham H.M., Li M., Kanoni S., Shrader P., Cavalcanti-Proença C., Kumari M., Qi L., Timpson N.J., Gieger C., Zabena C., Rocheleau G., Ingelsson E., An P., O'Connell J., Luan J., Elliott A., McCarroll S.A., Payne F., Roccasecca R.M., Pattou F., Sethupathy P., Ardlie K., Ariyurek Y., Balkau B., Barter P., Beilby J.P., Ben-Shlomo Y., Benediktsson R., Bennett A.J., Bergmann S., Bochud M., Boerwinkle E., Bonnefond A., Bonnycastle L.L., Borch-Johnsen K., Böttcher Y., Brunner E., Bumpstead S.J., Charpentier G., Chen Y.D., Chines P., Clarke R., Coin L.J., Cooper M.N., Cornelis M., Crawford G., Crisponi L., Day I.N., de Geus E.J., Delplanque J., Dina C., Erdos M.R., Fedson A.C., Fischer-Rosinsky A., Forouhi N.G., Fox C.S., Frants R., Franzosi M.G., Galan P., Goodarzi M.O., Graessler J., Groves C.J., Grundy S., Gwilliam R., Gyllensten U., Hadjadj S., Hallmans G., Hammond N., Han X., Hartikainen A.L., Hassanali N., Hayward C., Heath S.C., Hercberg S., Herder C., Hicks A.A., Hillman D.R., Hingorani A.D., Hofman A., Hui J., Hung J., Isomaa B., Johnson P.R., Jørgensen T., Jula A., Kaakinen M., Kaprio J., Kesaniemi Y.A., Kivimaki M., Knight B., Koskinen S., Kovacs P., Kyvik K.O., Lathrop G.M., Lawlor D.A., Le Bacquer O., Lecoeur C., Li Y., Lyssenko V., Mahley R., Mangino M., Manning A.K., Martínez-Larrad M.T., McAteer J.B., McCulloch L.J., McPherson R., Meisinger C., Melzer D., Meyre D., Mitchell B.D., Morken M.A., Mukherjee S., Naitza S., Narisu N., Neville M.J., Oostra B.A., Orrù M., Pakyz R., Palmer C.N., Paolisso G., Pattaro C., Pearson D., Peden J.F., Pedersen N.L., Perola M., Pfeiffer A.F., Pichler I., Polasek O., Posthuma D., Potter S.C., Pouta A., Province M.A., Psaty B.M., Rathmann W., Rayner N.W., Rice K., Ripatti S., Rivadeneira F., Roden M., Rolandsson O., Sandbaek A., Sandhu M., Sanna S., Sayer A.A., Scheet P., Scott L.J., Seedorf U., Sharp S.J., Shields B., Sigurethsson G., Sijbrands E.J., Silveira A., Simpson L., Singleton A., Smith N.L., Sovio U., Swift A., Syddall H., Syvänen A.C., Tanaka T., Thorand B., Tichet J., Tönjes A., Tuomi T., Uitterlinden A.G., van Dijk K.W., van Hoek M., Varma D., Visvikis-Siest S., Vitart V., Vogelzangs N., Waeber G., Wagner P.J., Walley A., Walters G.B., Ward K.L., Watkins H., Weedon M.N., Wild S.H., Willemsen G., Witteman J.C., Yarnell J.W., Zeggini E., Zelenika D., Zethelius B., Zhai G., Zhao J.H., Zillikens M.C., Borecki I.B., Loos R.J., Meneton P., Magnusson P.K., Nathan D.M., Williams G.H., Hattersley A.T., Silander K., Salomaa V., Smith G.D., Bornstein S.R., Schwarz P., Spranger J., Karpe F., Shuldiner A.R., Cooper C., Dedoussis G.V., Serrano-Ríos M., Morris A.D., Lind L., Palmer L.J., Hu F.B., Franks P.W., Ebrahim S., Marmot M., Kao W.H., Pankow J.S., Sampson M.J., Kuusisto J., Laakso M., Hansen T., Pedersen O., Pramstaller P.P., Wichmann H.E., Illig T., Rudan I., Wright A.F., Stumvoll M., Campbell H., Wilson J.F., Bergman R.N., Buchanan T.A., Collins F.S., Mohlke K.L., Tuomilehto J., Valle T.T., Altshuler D., Rotter J.I., Siscovick D.S., Penninx B.W., Boomsma D.I., Deloukas P., Spector T.D., Frayling T.M., Ferrucci L., Kong A., Thorsteinsdottir U., Stefansson K., van Duijn C.M., Aulchenko Y.S., Cao A., Scuteri A., Schlessinger D., Uda M., Ruokonen A., Jarvelin M.R., Waterworth D.M., Vollenweider P., Peltonen L., Mooser V., Abecasis G.R., Wareham N.J., Sladek R., Froguel P., Watanabe R.M., Meigs J.B., Groop L., Boehnke M., McCarthy M.I., Florez J.C., Barroso I.
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
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
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