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.
Original language | English |
---|---|
Pages (from-to) | 105-116 |
Number of pages | 12 |
Journal | Nature Genetics |
Volume | 42 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2010 |
Externally published | Yes |
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In: Nature Genetics, Vol. 42, No. 2, 02.2010, p. 105-116.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
AU - Dupuis, Josée
AU - Langenberg, Claudia
AU - Prokopenko, Inga
AU - Saxena, Richa
AU - Soranzo, Nicole
AU - Jackson, Anne U.
AU - Wheeler, Eleanor
AU - Glazer, Nicole L.
AU - Bouatia-Naji, Nabila
AU - Gloyn, Anna L.
AU - Lindgren, Cecilia M.
AU - Mägi, Reedik
AU - Morris, Andrew P.
AU - Randall, Joshua
AU - Johnson, Toby
AU - Elliott, Paul
AU - Rybin, Denis
AU - Thorleifsson, Gudmar
AU - Steinthorsdottir, Valgerdur
AU - Henneman, Peter
AU - Grallert, Harald
AU - Dehghan, Abbas
AU - JanHottenga, Jouke
AU - Franklin, Christopher S.
AU - Navarro, Pau
AU - Song, Kijoung
AU - Goel, Anuj
AU - Perry, John R.B.
AU - Egan, Josephine M.
AU - Lajunen, Taina
AU - Grarup, Niels
AU - Sparsø, Thomas
AU - Doney, Alex
AU - Voight, Benjamin F.
AU - Stringham, Heather M.
AU - Li, Man
AU - Kanoni, Stavroula
AU - Shrader, Peter
AU - Cavalcanti-Proença, Christine
AU - Kumari, Meena
AU - Qi, Lu
AU - Timpson, Nicholas J.
AU - Gieger, Christian
AU - Zabena, Carina
AU - Rocheleau, Ghislain
AU - Ingelsson, Erik
AU - An, Ping
AU - O'Connell, Jeffrey
AU - Luan, Jian'An
AU - Elliott, Amanda
AU - McCarroll, Steven A.
AU - Payne, Felicity
AU - Roccasecca, Rosa Maria
AU - Pattou, François
AU - Sethupathy, Praveen
AU - Ardlie, Kristin
AU - Ariyurek, Yavuz
AU - Balkau, Beverley
AU - Barter, Philip
AU - Beilby, John P.
AU - Ben-Shlomo, Yoav
AU - Benediktsson, Rafn
AU - Bennett, Amanda J.
AU - Bergmann, Sven
AU - Bochud, Murielle
AU - Boerwinkle, Eric
AU - Bonnefond, Amélie
AU - Bonnycastle, Lori L.
AU - Borch-Johnsen, Knut
AU - Böttcher, Yvonne
AU - Brunner, Eric
AU - Bumpstead, Suzannah J.
AU - Charpentier, Guillaume
AU - Der IdaChen, Yii
AU - Chines, Peter
AU - Clarke, Robert
AU - McOin, Lachlan J.
AU - Cooper, Matthew N.
AU - Cornelis, Marilyn
AU - Crawford, Gabe
AU - Crisponi, Laura
AU - Day, Ian N.M.
AU - De Geus, Eco J.C.
AU - Delplanque, Jerome
AU - Dina, Christian
AU - Erdos, Michael R.
AU - Fedson, Annette C.
AU - Fischer-Rosinsky, Antje
AU - Forouhi, Nita G.
AU - Fox, Caroline S.
AU - Frants, Rune
AU - GraziaFranzosi, Maria
AU - Galan, Pilar
AU - Goodarzi, Mark O.
AU - Graessler, Jürgen
AU - Groves, Christopher J.
AU - Grundy, Scott
AU - Gwilliam, Rhian
AU - Gyllensten, Ulf
AU - Hadjadj, Samy
AU - Hallmans, Göran
AU - Hammond, Naomi
AU - Han, Xijing
AU - -LiisaHartikainen, Anna
AU - Hassanali, Neelam
AU - Hayward, Caroline
AU - Heath, Simon C.
AU - Hercberg, Serge
AU - Herder, Christian
AU - Hicks, Andrew A.
AU - Hillman, David R.
AU - Hingorani, Aroon D.
AU - Hofman, Albert
AU - Hui, Jennie
AU - Hung, Joe
AU - Isomaa, Bo
AU - Johnson, Paul R.V.
AU - Jørgensen, Torben
AU - Jula, Antti
AU - Kaakinen, Marika
AU - Kaprio, Jaakko
AU - AnteroKesaniemi, Y.
AU - Kivimaki, Mika
AU - Knight, Beatrice
AU - Koskinen, Seppo
AU - Kovacs, Peter
AU - Kyvik, Kirsten Ohm
AU - Lathrop, G. Mark
AU - Lawlor, Debbie A.
AU - Bacquer, Olivier Le
AU - Lecoeur, Cécile
AU - Li, Yun
AU - Lyssenko, Valeriya
AU - Mahley, Robert
AU - Mangino, Massimo
AU - Manning, Alisa K.
AU - TeresaMartínez-Larrad, María
AU - McAteer, Jarred B.
AU - McCulloch, Laura J.
AU - McPherson, Ruth
AU - Meisinger, Christa
AU - Melzer, David
AU - Meyre, David
AU - Mitchell, Braxton D.
AU - Morken, Mario A.
AU - Mukherjee, Sutapa
AU - Naitza, Silvia
AU - Narisu, Narisu
AU - Neville, Matthew J.
AU - Oostra, Ben A.
AU - Orrù, Marco
AU - Pakyz, Ruth
AU - APalmer, Colin N.
AU - Paolisso, Giuseppe
AU - Pattaro, Cristian
AU - Pearson, Daniel
AU - Peden, John F.
AU - Pedersen, Nancy L.
AU - Perola, Markus
AU - Pfeiffer, Andreas F.H.
AU - Pichler, Irene
AU - Polasek, Ozren
AU - Posthuma, Danielle
AU - Potter, Simon C.
AU - Pouta, Anneli
AU - Province, Michael A.
AU - Psaty, Bruce M.
AU - Rathmann, Wolfgang
AU - Rayner, Nigel W.
AU - Rice, Kenneth
AU - Ripatti, Samuli
AU - Rivadeneira, Fernando
AU - Roden, Michael
AU - Rolandsson, Olov
AU - Sandbaek, Annelli
AU - Sandhu, Manjinder
AU - Sanna, Serena
AU - Sayer, Avan Aihie
AU - Scheet, Paul
AU - Scott, Laura J.
AU - Seedorf, Udo
AU - Sharp, Stephen J.
AU - Shields, Beverley
AU - Sigursson, Gunnar
AU - Sijbrands, Eric J.G.
AU - Silveira, Angela
AU - Simpson, Laila
AU - Singleton, Andrew
AU - Smith, Nicholas L.
AU - Sovio, Ulla
AU - Swift, Amy
AU - Syddall, Holly
AU - -ChristineSyvänen, Ann
AU - Tanaka, Toshiko
AU - Thorand, Barbara
AU - Tichet, Jean
AU - Tönjes, Anke
AU - Tuomi, Tiinamaija
AU - Uitterlinden, André G.
AU - Van Dijk, Ko Willems
AU - Hoek, Mandy Van
AU - Varma, Dhiraj
AU - Visvikis-Siest, Sophie
AU - Vitart, Veronique
AU - Vogelzangs, Nicole
AU - Waeber, Gérard
AU - Wagner, Peter J.
AU - Walley, Andrew
AU - BragiWalters, G.
AU - Ward, Kim L.
AU - Watkins, Hugh
AU - Weedon, Michael N.
AU - Wild, Sarah H.
AU - Willemsen, Gonneke
AU - MWitteman, Jaqueline C.
AU - GYarnell, John W.
AU - Zeggini, Eleftheria
AU - Zelenika, Diana
AU - Zethelius, Björn
AU - Zhai, Guangju
AU - Zhao, Jing Hua
AU - Zillikens, M. Carola
AU - Borecki, Ingrid B.
AU - Loos, Ruth J.F.
AU - Meneton, Pierre
AU - Magnusson, Patrik K.E.
AU - Nathan, David M.
AU - Williams, Gordon H.
AU - Hattersley, Andrew T.
AU - Silander, Kaisa
AU - Salomaa, Veikko
AU - Smith, George Davey
AU - Bornstein, Stefan R.
AU - Schwarz, Peter
AU - Spranger, Joachim
AU - Karpe, Fredrik
AU - Shuldiner, Alan R.
AU - Cooper, Cyrus
AU - Dedoussis, George V.
AU - Serrano-Ríos, Manuel
AU - Morris, Andrew D.
AU - Lind, Lars
AU - Palmer, Lyle J.
AU - Hu, Frank B.
AU - Franks, Paul W.
AU - Ebrahim, Shah
AU - Marmot, Michael
AU - Linda Kao, W. H.
AU - Pankow, James S.
AU - Sampson, Michael J.
AU - Kuusisto, Johanna
AU - Laakso, Markku
AU - Hansen, Torben
AU - Pedersen, Oluf
AU - Pramstaller, Peter Paul
AU - Wichmann, H. Erich
AU - Illig, Thomas
AU - Rudan, Igor
AU - Wright, Alan F.
AU - Stumvoll, Michael
AU - Campbell, Harry
AU - Wilson, James F.
AU - Bergman, Richard N.
AU - Buchanan, Thomas A.
AU - Collins, Francis S.
AU - Mohlke, Karen L.
AU - Tuomilehto, Jaakko
AU - Valle, Timo T.
AU - Altshuler, David
AU - Rotter, Jerome I.
AU - Siscovick, David S.
AU - Penninx, Brenda W.J.H.
AU - Boomsma, Dorret I.
AU - Deloukas, Panos
AU - Spector, Timothy D.
AU - Frayling, Timothy M.
AU - Ferrucci, Luigi
AU - Kong, Augustine
AU - Thorsteinsdottir, Unnur
AU - Stefansson, Kari
AU - Van Duijn, Cornelia M.
AU - Aulchenko, Yurii S.
AU - Cao, Antonio
AU - Scuteri, Angelo
AU - Schlessinger, David
AU - Uda, Manuela
AU - Ruokonen, Aimo
AU - -RiittaJarvelin, Marjo
AU - Waterworth, Dawn M.
AU - Vollenweider, Peter
AU - Peltonen, Leena
AU - Mooser, Vincent
AU - Abecasis, Goncalo R.
AU - Wareham, Nicholas J.
AU - Sladek, Robert
AU - Froguel, Philippe
AU - Watanabe, Richard M.
AU - Meigs, James B.
AU - Groop, Leif
AU - Boehnke, Michael
AU - McCarthy, Mark I.
AU - Florez, Jose C.
AU - Barroso, Inês
PY - 2010/2
Y1 - 2010/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=75749086085&partnerID=8YFLogxK
U2 - 10.1038/ng.520
DO - 10.1038/ng.520
M3 - Article
AN - SCOPUS:75749086085
SN - 1061-4036
VL - 42
SP - 105
EP - 116
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -