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

2.50
Hdl Handle:
http://hdl.handle.net/2336/93938
Title:
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
Authors:
Dupuis, Josée; Langenberg, Claudia; Prokopenko, Inga; Saxena, Richa; Soranzo, Nicole; Jackson, Anne U; Wheeler, Eleanor; Glazer, Nicole L; Bouatia-Naji, Nabila; Gloyn, Anna L; Lindgren, Cecilia M; Mägi, Reedik; Morris, Andrew P; Randall, Joshua; Johnson, Toby; Elliott, Paul; Rybin, Denis; Thorleifsson, Gudmar; Steinthorsdottir, Valgerdur; Henneman, Peter; Grallert, Harald; Dehghan, Abbas; Hottenga, Jouke Jan; Franklin, Christopher S; Navarro, Pau; Song, Kijoung; Goel, Anuj; Perry, John R B; Egan, Josephine M; Lajunen, Taina; Grarup, Niels; Sparsø, Thomas; Doney, Alex; Voight, Benjamin F; Stringham, Heather M; Li, Man; Kanoni, Stavroula; Shrader, Peter; Cavalcanti-Proença, Christine; Kumari, Meena; Qi, Lu; Timpson, Nicholas J; Gieger, Christian; Zabena, Carina; Rocheleau, Ghislain; Ingelsson, Erik; An, Ping; O'Connell, Jeffrey; Luan, Jian'an; Elliott, Amanda; McCarroll, Steven A; Payne, Felicity; Roccasecca, Rosa Maria; Pattou, François; Sethupathy, Praveen; Ardlie, Kristin; Ariyurek, Yavuz; Balkau, Beverley; Barter, Philip; Beilby, John P; Ben-Shlomo, Yoav; Benediktsson, Rafn; Bennett, Amanda J; Bergmann, Sven; Bochud, Murielle; Boerwinkle, Eric; Bonnefond, Amélie; Bonnycastle, Lori L; Borch-Johnsen, Knut; Böttcher, Yvonne; Brunner, Eric; Bumpstead, Suzannah J; Charpentier, Guillaume; Chen, Yii-Der Ida; Chines, Peter; Clarke, Robert; Coin, Lachlan J M; Cooper, Matthew N; Cornelis, Marilyn; Crawford, Gabe; Crisponi, Laura; Day, Ian N M; de Geus, Eco J C; Delplanque, Jerome; Dina, Christian; Erdos, Michael R; Fedson, Annette C; Fischer-Rosinsky, Antje; Forouhi, Nita G; Fox, Caroline S; Frants, Rune; Franzosi, Maria Grazia; Galan, Pilar; Goodarzi, Mark O; Graessler, Jürgen; Groves, Christopher J; Grundy, Scott; Gwilliam, Rhian; Gyllensten, Ulf; Hadjadj, Samy; Hallmans, Göran; Hammond, Naomi; Han, Xijing; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hayward, Caroline; Heath, Simon C; Hercberg, Serge; Herder, Christian; Hicks, Andrew A; Hillman, David R; Hingorani, Aroon D; Hofman, Albert; Hui, Jennie; Hung, Joe; Isomaa, Bo; Johnson, Paul R V; Jørgensen, Torben; Jula, Antti; Kaakinen, Marika; Kaprio, Jaakko; Kesaniemi, Y Antero; Kivimaki, Mika; Knight, Beatrice; Koskinen, Seppo; Kovacs, Peter; Kyvik, Kirsten Ohm; Lathrop, G Mark; Lawlor, Debbie A; Le Bacquer, Olivier; Lecoeur, Cécile; Li, Yun; Lyssenko, Valeriya; Mahley, Robert; Mangino, Massimo; Manning, Alisa K; Martínez-Larrad, María Teresa; McAteer, Jarred B; McCulloch, Laura J; McPherson, Ruth; Meisinger, Christa; Melzer, David; Meyre, David; Mitchell, Braxton D; Morken, Mario A; Mukherjee, Sutapa; Naitza, Silvia; Narisu, Narisu; Neville, Matthew J; Oostra, Ben A; Orrù, Marco; Pakyz, Ruth; Palmer, Colin N A; Paolisso, Giuseppe; Pattaro, Cristian; Pearson, Daniel; Peden, John F; Pedersen, Nancy L; Perola, Markus; Pfeiffer, Andreas F H; Pichler, Irene; Polasek, Ozren; Posthuma, Danielle; Potter, Simon C; Pouta, Anneli; Province, Michael A; Psaty, Bruce M; Rathmann, Wolfgang; Rayner, Nigel W; Rice, Kenneth; Ripatti, Samuli; Rivadeneira, Fernando; Roden, Michael; Rolandsson, Olov; Sandbaek, Annelli; Sandhu, Manjinder; Sanna, Serena; Sayer, Avan Aihie; Scheet, Paul; Scott, Laura J; Seedorf, Udo; Sharp, Stephen J; Shields, Beverley; Sigurdsson, Gunnar; Sijbrands, Eric J G; Silveira, Angela; Simpson, Laila; Singleton, Andrew; Smith, Nicholas L; Sovio, Ulla; Swift, Amy; Syddall, Holly; Syvänen, Ann-Christine; Tanaka, Toshiko; Thorand, Barbara; Tichet, Jean; Tönjes, Anke; Tuomi, Tiinamaija; Uitterlinden, André G; van Dijk, Ko Willems; van Hoek, Mandy; Varma, Dhiraj; Visvikis-Siest, Sophie; Vitart, Veronique; Vogelzangs, Nicole; Waeber, Gérard; Wagner, Peter J; Walley, Andrew; Walters, G Bragi; Ward, Kim L; Watkins, Hugh; Weedon, Michael N; Wild, Sarah H; Willemsen, Gonneke; Witteman, Jaqueline C M; Yarnell, John W G; Zeggini, Eleftheria; Zelenika, Diana; Zethelius, Björn; Zhai, Guangju; Zhao, Jing Hua; Zillikens, M Carola; Borecki, Ingrid B; Loos, Ruth J F; Meneton, Pierre; Magnusson, Patrik K E; Nathan, David M; Williams, Gordon H; Hattersley, Andrew T; Silander, Kaisa; Salomaa, Veikko; Smith, George Davey; Bornstein, Stefan R; Schwarz, Peter; Spranger, Joachim; Karpe, Fredrik; Shuldiner, Alan R; Cooper, Cyrus; Dedoussis, George V; Serrano-Ríos, Manuel; Morris, Andrew D; Lind, Lars; Palmer, Lyle J; Hu, Frank B; Franks, Paul W; Ebrahim, Shah; Marmot, Michael; Kao, W H Linda; Pankow, James S; Sampson, Michael J; Kuusisto, Johanna; Laakso, Markku; Hansen, Torben; Pedersen, Oluf; Pramstaller, Peter Paul; Wichmann, H Erich; Illig, Thomas; Rudan, Igor; Wright, Alan F; Stumvoll, Michael; Campbell, Harry; Wilson, James F; Bergman, Richard N; Buchanan, Thomas A; Collins, Francis S; Mohlke, Karen L; Tuomilehto, Jaakko; Valle, Timo T; Altshuler, David; Rotter, Jerome I; Siscovick, David S; Penninx, Brenda W J H; Boomsma, Dorret I; Deloukas, Panos; Spector, Timothy D; Frayling, Timothy M; Ferrucci, Luigi; Kong, Augustine; Thorsteinsdottir, Unnur; Stefansson, Kari; van Duijn, Cornelia M; Aulchenko, Yurii S; Cao, Antonio; Scuteri, Angelo; Schlessinger, David; Uda, Manuela; Ruokonen, Aimo; Jarvelin, Marjo-Riitta; Waterworth, Dawn M; Vollenweider, Peter; Peltonen, Leena; Mooser, Vincent; Abecasis, Goncalo R; Wareham, Nicholas J; Sladek, Robert; Froguel, Philippe; Watanabe, Richard M; Meigs, James B; Groop, Leif; Boehnke, Michael; McCarthy, Mark I; Florez, Jose C; Barroso, Inês
Citation:
Nat. Genet. 2010, 42(2):105-16
Issue Date:
1-Feb-2010
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.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://dx.doi.org/10.1038/ng.520

Full metadata record

DC FieldValue Language
dc.contributor.authorDupuis, Joséeen
dc.contributor.authorLangenberg, Claudiaen
dc.contributor.authorProkopenko, Ingaen
dc.contributor.authorSaxena, Richaen
dc.contributor.authorSoranzo, Nicoleen
dc.contributor.authorJackson, Anne Uen
dc.contributor.authorWheeler, Eleanoren
dc.contributor.authorGlazer, Nicole Len
dc.contributor.authorBouatia-Naji, Nabilaen
dc.contributor.authorGloyn, Anna Len
dc.contributor.authorLindgren, Cecilia Men
dc.contributor.authorMägi, Reediken
dc.contributor.authorMorris, Andrew Pen
dc.contributor.authorRandall, Joshuaen
dc.contributor.authorJohnson, Tobyen
dc.contributor.authorElliott, Paulen
dc.contributor.authorRybin, Denisen
dc.contributor.authorThorleifsson, Gudmaren
dc.contributor.authorSteinthorsdottir, Valgerduren
dc.contributor.authorHenneman, Peteren
dc.contributor.authorGrallert, Haralden
dc.contributor.authorDehghan, Abbasen
dc.contributor.authorHottenga, Jouke Janen
dc.contributor.authorFranklin, Christopher Sen
dc.contributor.authorNavarro, Pauen
dc.contributor.authorSong, Kijoungen
dc.contributor.authorGoel, Anujen
dc.contributor.authorPerry, John R Ben
dc.contributor.authorEgan, Josephine Men
dc.contributor.authorLajunen, Tainaen
dc.contributor.authorGrarup, Nielsen
dc.contributor.authorSparsø, Thomasen
dc.contributor.authorDoney, Alexen
dc.contributor.authorVoight, Benjamin Fen
dc.contributor.authorStringham, Heather Men
dc.contributor.authorLi, Manen
dc.contributor.authorKanoni, Stavroulaen
dc.contributor.authorShrader, Peteren
dc.contributor.authorCavalcanti-Proença, Christineen
dc.contributor.authorKumari, Meenaen
dc.contributor.authorQi, Luen
dc.contributor.authorTimpson, Nicholas Jen
dc.contributor.authorGieger, Christianen
dc.contributor.authorZabena, Carinaen
dc.contributor.authorRocheleau, Ghislainen
dc.contributor.authorIngelsson, Eriken
dc.contributor.authorAn, Pingen
dc.contributor.authorO'Connell, Jeffreyen
dc.contributor.authorLuan, Jian'anen
dc.contributor.authorElliott, Amandaen
dc.contributor.authorMcCarroll, Steven Aen
dc.contributor.authorPayne, Felicityen
dc.contributor.authorRoccasecca, Rosa Mariaen
dc.contributor.authorPattou, Françoisen
dc.contributor.authorSethupathy, Praveenen
dc.contributor.authorArdlie, Kristinen
dc.contributor.authorAriyurek, Yavuzen
dc.contributor.authorBalkau, Beverleyen
dc.contributor.authorBarter, Philipen
dc.contributor.authorBeilby, John Pen
dc.contributor.authorBen-Shlomo, Yoaven
dc.contributor.authorBenediktsson, Rafnen
dc.contributor.authorBennett, Amanda Jen
dc.contributor.authorBergmann, Svenen
dc.contributor.authorBochud, Murielleen
dc.contributor.authorBoerwinkle, Ericen
dc.contributor.authorBonnefond, Amélieen
dc.contributor.authorBonnycastle, Lori Len
dc.contributor.authorBorch-Johnsen, Knuten
dc.contributor.authorBöttcher, Yvonneen
dc.contributor.authorBrunner, Ericen
dc.contributor.authorBumpstead, Suzannah Jen
dc.contributor.authorCharpentier, Guillaumeen
dc.contributor.authorChen, Yii-Der Idaen
dc.contributor.authorChines, Peteren
dc.contributor.authorClarke, Roberten
dc.contributor.authorCoin, Lachlan J Men
dc.contributor.authorCooper, Matthew Nen
dc.contributor.authorCornelis, Marilynen
dc.contributor.authorCrawford, Gabeen
dc.contributor.authorCrisponi, Lauraen
dc.contributor.authorDay, Ian N Men
dc.contributor.authorde Geus, Eco J Cen
dc.contributor.authorDelplanque, Jeromeen
dc.contributor.authorDina, Christianen
dc.contributor.authorErdos, Michael Ren
dc.contributor.authorFedson, Annette Cen
dc.contributor.authorFischer-Rosinsky, Antjeen
dc.contributor.authorForouhi, Nita Gen
dc.contributor.authorFox, Caroline Sen
dc.contributor.authorFrants, Runeen
dc.contributor.authorFranzosi, Maria Graziaen
dc.contributor.authorGalan, Pilaren
dc.contributor.authorGoodarzi, Mark Oen
dc.contributor.authorGraessler, Jürgenen
dc.contributor.authorGroves, Christopher Jen
dc.contributor.authorGrundy, Scotten
dc.contributor.authorGwilliam, Rhianen
dc.contributor.authorGyllensten, Ulfen
dc.contributor.authorHadjadj, Samyen
dc.contributor.authorHallmans, Göranen
dc.contributor.authorHammond, Naomien
dc.contributor.authorHan, Xijingen
dc.contributor.authorHartikainen, Anna-Liisaen
dc.contributor.authorHassanali, Neelamen
dc.contributor.authorHayward, Carolineen
dc.contributor.authorHeath, Simon Cen
dc.contributor.authorHercberg, Sergeen
dc.contributor.authorHerder, Christianen
dc.contributor.authorHicks, Andrew Aen
dc.contributor.authorHillman, David Ren
dc.contributor.authorHingorani, Aroon Den
dc.contributor.authorHofman, Alberten
dc.contributor.authorHui, Jennieen
dc.contributor.authorHung, Joeen
dc.contributor.authorIsomaa, Boen
dc.contributor.authorJohnson, Paul R Ven
dc.contributor.authorJørgensen, Torbenen
dc.contributor.authorJula, Anttien
dc.contributor.authorKaakinen, Marikaen
dc.contributor.authorKaprio, Jaakkoen
dc.contributor.authorKesaniemi, Y Anteroen
dc.contributor.authorKivimaki, Mikaen
dc.contributor.authorKnight, Beatriceen
dc.contributor.authorKoskinen, Seppoen
dc.contributor.authorKovacs, Peteren
dc.contributor.authorKyvik, Kirsten Ohmen
dc.contributor.authorLathrop, G Marken
dc.contributor.authorLawlor, Debbie Aen
dc.contributor.authorLe Bacquer, Olivieren
dc.contributor.authorLecoeur, Cécileen
dc.contributor.authorLi, Yunen
dc.contributor.authorLyssenko, Valeriyaen
dc.contributor.authorMahley, Roberten
dc.contributor.authorMangino, Massimoen
dc.contributor.authorManning, Alisa Ken
dc.contributor.authorMartínez-Larrad, María Teresaen
dc.contributor.authorMcAteer, Jarred Ben
dc.contributor.authorMcCulloch, Laura Jen
dc.contributor.authorMcPherson, Ruthen
dc.contributor.authorMeisinger, Christaen
dc.contributor.authorMelzer, Daviden
dc.contributor.authorMeyre, Daviden
dc.contributor.authorMitchell, Braxton Den
dc.contributor.authorMorken, Mario Aen
dc.contributor.authorMukherjee, Sutapaen
dc.contributor.authorNaitza, Silviaen
dc.contributor.authorNarisu, Narisuen
dc.contributor.authorNeville, Matthew Jen
dc.contributor.authorOostra, Ben Aen
dc.contributor.authorOrrù, Marcoen
dc.contributor.authorPakyz, Ruthen
dc.contributor.authorPalmer, Colin N Aen
dc.contributor.authorPaolisso, Giuseppeen
dc.contributor.authorPattaro, Cristianen
dc.contributor.authorPearson, Danielen
dc.contributor.authorPeden, John Fen
dc.contributor.authorPedersen, Nancy Len
dc.contributor.authorPerola, Markusen
dc.contributor.authorPfeiffer, Andreas F Hen
dc.contributor.authorPichler, Ireneen
dc.contributor.authorPolasek, Ozrenen
dc.contributor.authorPosthuma, Danielleen
dc.contributor.authorPotter, Simon Cen
dc.contributor.authorPouta, Annelien
dc.contributor.authorProvince, Michael Aen
dc.contributor.authorPsaty, Bruce Men
dc.contributor.authorRathmann, Wolfgangen
dc.contributor.authorRayner, Nigel Wen
dc.contributor.authorRice, Kennethen
dc.contributor.authorRipatti, Samulien
dc.contributor.authorRivadeneira, Fernandoen
dc.contributor.authorRoden, Michaelen
dc.contributor.authorRolandsson, Oloven
dc.contributor.authorSandbaek, Annellien
dc.contributor.authorSandhu, Manjinderen
dc.contributor.authorSanna, Serenaen
dc.contributor.authorSayer, Avan Aihieen
dc.contributor.authorScheet, Paulen
dc.contributor.authorScott, Laura Jen
dc.contributor.authorSeedorf, Udoen
dc.contributor.authorSharp, Stephen Jen
dc.contributor.authorShields, Beverleyen
dc.contributor.authorSigurdsson, Gunnaren
dc.contributor.authorSijbrands, Eric J Gen
dc.contributor.authorSilveira, Angelaen
dc.contributor.authorSimpson, Lailaen
dc.contributor.authorSingleton, Andrewen
dc.contributor.authorSmith, Nicholas Len
dc.contributor.authorSovio, Ullaen
dc.contributor.authorSwift, Amyen
dc.contributor.authorSyddall, Hollyen
dc.contributor.authorSyvänen, Ann-Christineen
dc.contributor.authorTanaka, Toshikoen
dc.contributor.authorThorand, Barbaraen
dc.contributor.authorTichet, Jeanen
dc.contributor.authorTönjes, Ankeen
dc.contributor.authorTuomi, Tiinamaijaen
dc.contributor.authorUitterlinden, André Gen
dc.contributor.authorvan Dijk, Ko Willemsen
dc.contributor.authorvan Hoek, Mandyen
dc.contributor.authorVarma, Dhirajen
dc.contributor.authorVisvikis-Siest, Sophieen
dc.contributor.authorVitart, Veroniqueen
dc.contributor.authorVogelzangs, Nicoleen
dc.contributor.authorWaeber, Gérarden
dc.contributor.authorWagner, Peter Jen
dc.contributor.authorWalley, Andrewen
dc.contributor.authorWalters, G Bragien
dc.contributor.authorWard, Kim Len
dc.contributor.authorWatkins, Hughen
dc.contributor.authorWeedon, Michael Nen
dc.contributor.authorWild, Sarah Hen
dc.contributor.authorWillemsen, Gonnekeen
dc.contributor.authorWitteman, Jaqueline C Men
dc.contributor.authorYarnell, John W Gen
dc.contributor.authorZeggini, Eleftheriaen
dc.contributor.authorZelenika, Dianaen
dc.contributor.authorZethelius, Björnen
dc.contributor.authorZhai, Guangjuen
dc.contributor.authorZhao, Jing Huaen
dc.contributor.authorZillikens, M Carolaen
dc.contributor.authorBorecki, Ingrid Ben
dc.contributor.authorLoos, Ruth J Fen
dc.contributor.authorMeneton, Pierreen
dc.contributor.authorMagnusson, Patrik K Een
dc.contributor.authorNathan, David Men
dc.contributor.authorWilliams, Gordon Hen
dc.contributor.authorHattersley, Andrew Ten
dc.contributor.authorSilander, Kaisaen
dc.contributor.authorSalomaa, Veikkoen
dc.contributor.authorSmith, George Daveyen
dc.contributor.authorBornstein, Stefan Ren
dc.contributor.authorSchwarz, Peteren
dc.contributor.authorSpranger, Joachimen
dc.contributor.authorKarpe, Fredriken
dc.contributor.authorShuldiner, Alan Ren
dc.contributor.authorCooper, Cyrusen
dc.contributor.authorDedoussis, George Ven
dc.contributor.authorSerrano-Ríos, Manuelen
dc.contributor.authorMorris, Andrew Den
dc.contributor.authorLind, Larsen
dc.contributor.authorPalmer, Lyle Jen
dc.contributor.authorHu, Frank Ben
dc.contributor.authorFranks, Paul Wen
dc.contributor.authorEbrahim, Shahen
dc.contributor.authorMarmot, Michaelen
dc.contributor.authorKao, W H Lindaen
dc.contributor.authorPankow, James Sen
dc.contributor.authorSampson, Michael Jen
dc.contributor.authorKuusisto, Johannaen
dc.contributor.authorLaakso, Markkuen
dc.contributor.authorHansen, Torbenen
dc.contributor.authorPedersen, Olufen
dc.contributor.authorPramstaller, Peter Paulen
dc.contributor.authorWichmann, H Erichen
dc.contributor.authorIllig, Thomasen
dc.contributor.authorRudan, Igoren
dc.contributor.authorWright, Alan Fen
dc.contributor.authorStumvoll, Michaelen
dc.contributor.authorCampbell, Harryen
dc.contributor.authorWilson, James Fen
dc.contributor.authorBergman, Richard Nen
dc.contributor.authorBuchanan, Thomas Aen
dc.contributor.authorCollins, Francis Sen
dc.contributor.authorMohlke, Karen Len
dc.contributor.authorTuomilehto, Jaakkoen
dc.contributor.authorValle, Timo Ten
dc.contributor.authorAltshuler, Daviden
dc.contributor.authorRotter, Jerome Ien
dc.contributor.authorSiscovick, David Sen
dc.contributor.authorPenninx, Brenda W J Hen
dc.contributor.authorBoomsma, Dorret Ien
dc.contributor.authorDeloukas, Panosen
dc.contributor.authorSpector, Timothy Den
dc.contributor.authorFrayling, Timothy Men
dc.contributor.authorFerrucci, Luigien
dc.contributor.authorKong, Augustineen
dc.contributor.authorThorsteinsdottir, Unnuren
dc.contributor.authorStefansson, Karien
dc.contributor.authorvan Duijn, Cornelia Men
dc.contributor.authorAulchenko, Yurii Sen
dc.contributor.authorCao, Antonioen
dc.contributor.authorScuteri, Angeloen
dc.contributor.authorSchlessinger, Daviden
dc.contributor.authorUda, Manuelaen
dc.contributor.authorRuokonen, Aimoen
dc.contributor.authorJarvelin, Marjo-Riittaen
dc.contributor.authorWaterworth, Dawn Men
dc.contributor.authorVollenweider, Peteren
dc.contributor.authorPeltonen, Leenaen
dc.contributor.authorMooser, Vincenten
dc.contributor.authorAbecasis, Goncalo Ren
dc.contributor.authorWareham, Nicholas Jen
dc.contributor.authorSladek, Roberten
dc.contributor.authorFroguel, Philippeen
dc.contributor.authorWatanabe, Richard Men
dc.contributor.authorMeigs, James Ben
dc.contributor.authorGroop, Leifen
dc.contributor.authorBoehnke, Michaelen
dc.contributor.authorMcCarthy, Mark Ien
dc.contributor.authorFlorez, Jose Cen
dc.contributor.authorBarroso, Inêsen
dc.date.accessioned2010-03-09T11:25:03Z-
dc.date.available2010-03-09T11:25:03Z-
dc.date.issued2010-02-01-
dc.date.submitted2010-03-09-
dc.identifier.citationNat. Genet. 2010, 42(2):105-16en
dc.identifier.issn1546-1718-
dc.identifier.pmid20081858-
dc.identifier.doi10.1038/ng.520-
dc.identifier.urihttp://hdl.handle.net/2336/93938-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
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.en
dc.language.isoenen
dc.publisherNature Pub. Coen
dc.relation.urlhttp://dx.doi.org/10.1038/ng.520en
dc.subject.meshAdolescenten
dc.subject.meshAdulten
dc.subject.meshAllelesen
dc.subject.meshBlood Glucoseen
dc.subject.meshChilden
dc.subject.meshDNA Copy Number Variationsen
dc.subject.meshDatabases, Geneticen
dc.subject.meshDiabetes Mellitus, Type 2en
dc.subject.meshFastingen
dc.subject.meshGene Expression Regulationen
dc.subject.meshGenetic Locien
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshGenome-Wide Association Studyen
dc.subject.meshHomeostasisen
dc.subject.meshHumansen
dc.subject.meshMeta-Analysis as Topicen
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshQuantitative Trait Locien
dc.subject.meshQuantitative Trait, Heritableen
dc.subject.meshReproducibility of Resultsen
dc.titleNew genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risken
dc.typeArticleen
dc.contributor.departmentDepartment of Biostatistics, Boston University School of Public Health, Massachusetts, USA.en
dc.identifier.journalNature geneticsen

Related articles on PubMed

All Items in Hirsla are protected by copyright, with all rights reserved, unless otherwise indicated.