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

Autoria(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.; DIAGRAM Consortium; GIANT Consortium; Global BPgen Consortium; Borecki I.B.; 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.; Anders Hamsten on behalf of Procardis Consortium; MAGIC investigators; Bergman R.N.; 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.
Data(s)

2010
Resumo

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.
Identificador

https://serval.unil.ch/?id=serval:BIB_68555FB264D9

isbn:1546-1718[electronic], 1061-4036[linking]

pmid:20081858

doi:10.1038/ng.520

isiid:000274084400005
Idioma(s)

en
Fonte

Nature Genetics, vol. 42, no. 2, pp. 105-116
Palavras-Chave #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 ; Colaus Study
Tipo

info:eu-repo/semantics/article

article
Acesso ao item digital