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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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Nature Genetics
volume
42
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2
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32 - 105
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Nature Publishing Group
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  • wos:000274084400005
  • scopus:75749086085
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1546-1718
DOI
10.1038/ng.520
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English
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cbc17f48-40b8-4e72-a86f-bccd53b90a44 (old id 1569532)
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2010-03-17 09:46:55
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@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. 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  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},
  volume       = {42},
  year         = {2010},
}