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

Dupuis, Josee ; Langenberg, Claudia ; Prokopenko, Inga ; Saxena, Richa ; Soranzo, Nicole ; Jackson, Anne U. ; Wheeler, Eleanor ; Glazer, Nicole L. ; Bouatia-Naji, Nabila and Gloyn, Anna L. , et al. (2010) In Nature Genetics 42(2). p.32-105
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... (More)
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. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Genetics
volume
42
issue
2
pages
32 - 105
publisher
Nature Publishing Group
external identifiers
  • wos:000274084400005
  • scopus:75749086085
  • pmid:20081858
ISSN
1546-1718
DOI
10.1038/ng.520
language
English
LU publication?
yes
id
cbc17f48-40b8-4e72-a86f-bccd53b90a44 (old id 1569532)
date added to LUP
2016-04-01 13:04:55
date last changed
2024-05-09 00:03:51
@article{cbc17f48-40b8-4e72-a86f-bccd53b90a44,
  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.}},
  author       = {{Dupuis, Josee and Langenberg, Claudia and Prokopenko, Inga and Saxena, Richa and Soranzo, Nicole and Jackson, Anne U. and Wheeler, Eleanor and Glazer, Nicole L. and Bouatia-Naji, Nabila and Gloyn, Anna L. and Lindgren, Cecilia M. and Magi, Reedik and Morris, Andrew P. and Randall, Joshua and Johnson, Toby and Elliott, Paul and Rybin, Denis and Thorleifsson, Gudmar and Steinthorsdottir, Valgerdur and Henneman, Peter and Grallert, Harald and Dehghan, Abbas and Hottenga, Jouke Jan and Franklin, Christopher S. and Navarro, Pau and Song, Kijoung and Goel, Anuj and Perry, John R. B. and Egan, Josephine M. and Lajunen, Taina and Grarup, Niels and Sparso, Thomas and Doney, Alex and Voight, Benjamin F. and Stringham, Heather M. and Li, Man and Kanoni, Stavroula and Shrader, Peter and Cavalcanti-Proenca, Christine and Kumari, Meena and Qi, Lu and Timpson, Nicholas J. and Gieger, Christian and Zabena, Carina and Rocheleau, Ghislain and Ingelsson, Erik and An, Ping and O'Connell, Jeffrey and Luan, Jian'an and Elliott, Amanda and McCarroll, Steven A. and Payne, Felicity and Roccasecca, Rosa Maria and Pattou, Francois and Sethupathy, Praveen and Ardlie, Kristin and Ariyurek, Yavuz and Balkau, Beverley and Barter, Philip and Beilby, John P. and Ben-Shlomo, Yoav and Benediktsson, Rafn and Bennett, Amanda J. and Bergmann, Sven and Bochud, Murielle and Boerwinkle, Eric and Bonnefond, Amelie and Bonnycastle, Lori L. and Borch-Johnsen, Knut and Boettcher, Yvonne and Brunner, Eric and Bumpstead, Suzannah J. and Charpentier, Guillaume and Chen, Yii-Der Ida and Chines, Peter and Clarke, Robert and Coin, Lachlan J. M. and Cooper, Matthew N. and Cornelis, Marilyn and Crawford, Gabe and Crisponi, Laura and Day, Ian N. M. and de Geus, Eco J. C. and Delplanque, Jerome and Dina, Christian and Erdos, Michael R. and Fedson, Annette C. and Fischer-Rosinsky, Antje and Forouhi, Nita G. and Fox, Caroline S. and Frants, Rune and Franzosi, Maria Grazia and Galan, Pilar and Goodarzi, Mark O. and Graessler, Juergen and Groves, Christopher J. and Grundy, Scott and Gwilliam, Rhian and Gyllensten, Ulf and Hadjadj, Samy and Hallmans, Goeran and Hammond, Naomi and Han, Xijing and Hartikainen, Anna-Liisa and Hassanali, Neelam and Hayward, Caroline and Heath, Simon C. and Hercberg, Serge and Herder, Christian and Hicks, Andrew A. and Hillman, David R. and Hingorani, Aroon D. and Hofman, Albert and Hui, Jennie and Hung, Joe and Isomaa, Bo and Johnson, Paul R. V. and Jorgensen, Torben and Jula, Antti and Kaakinen, Marika and Kaprio, Jaakko and Kesaniemi, Y. 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H. and Boomsma, Dorret I. and Deloukas, Panos and Spector, Timothy D. and Frayling, Timothy M. and Ferrucci, Luigi and Kong, Augustine and Thorsteinsdottir, Unnur and Stefansson, Kari and van Duijn, Cornelia M. and Aulchenko, Yurii S. and Cao, Antonio and Scuteri, Angelo and Schlessinger, David and Uda, Manuela and Ruokonen, Aimo and Jarvelin, Marjo-Riitta and Waterworth, Dawn M. and Vollenweider, Peter and Peltonen, Leena and Mooser, Vincent and Abecasis, Goncalo R. and Wareham, Nicholas J. and Sladek, Robert and Froguel, Philippe and Watanabe, Richard M. and Meigs, James B. and Groop, Leif and Boehnke, Michael and McCarthy, Mark I. and Florez, Jose C. and Barroso, Ines}},
  issn         = {{1546-1718}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{32--105}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Genetics}},
  title        = {{New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk}},
  url          = {{http://dx.doi.org/10.1038/ng.520}},
  doi          = {{10.1038/ng.520}},
  volume       = {{42}},
  year         = {{2010}},
}