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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

Scott, Robert A.; Lagou, Vasiliki; Welch, Ryan P.; Wheeler, Eleanor; Montasser, May E.; Luan, Jian'an; Maegi, Reedik; Strawbridge, Rona J.; Rehnberg, Emil and Gustafsson, Stefan, et al. (2012) In Nature Genetics 44(9). p.991-991
Abstract
Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally... (More)
Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control. (Less)
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Nature Genetics
volume
44
issue
9
pages
991 - 991
publisher
Nature Publishing Group
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  • wos:000308491200010
  • scopus:84865693929
ISSN
1546-1718
DOI
10.1038/ng.2385
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English
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0ef9bf29-b272-4fdd-9203-e7a36d754113 (old id 3139506)
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2012-11-01 11:17:47
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@article{0ef9bf29-b272-4fdd-9203-e7a36d754113,
  abstract     = {Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q &lt; 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.},
  author       = {Scott, Robert A. and Lagou, Vasiliki and Welch, Ryan P. and Wheeler, Eleanor and Montasser, May E. and Luan, Jian'an and Maegi, Reedik and Strawbridge, Rona J. and Rehnberg, Emil and Gustafsson, Stefan and Kanoni, Stavroula and Rasmussen-Torvik, Laura J. and Yengo, Loic and Lecoeur, Cecile and Shungin, Dmitry and Sanna, Serena and Sidore, Carlo and Johnson, Paul C. D. and Jukema, J. Wouter and Johnson, Toby and Mahajan, Anubha and Verweij, Niek and Thorleifsson, Gudmar and Hottenga, Jouke-Jan and Shah, Sonia and Smith, Albert V. and Sennblad, Bengt and Gieger, Christian and Salo, Perttu and Perola, Markus and Timpson, Nicholas J. and Evans, David M. and St Pourcain, Beate and Wu, Ying and Andrews, Jeanette S. and Hui, Jennie and Bielak, Lawrence F. and Zhao, Wei and Horikoshi, Momoko and Navarro, Pau and Isaacs, Aaron and O'Connell, Jeffrey R. and Stirrups, Kathleen and Vitart, Veronique and Hayward, Caroline and Esko, Tonu and Mihailov, Evelin and Fraser, Ross M. and Fall, Tove and Voight, Benjamin F. and Raychaudhuri, Soumya and Chen, Han and Lindgren, Cecilia M. and Morris, Andrew P. and Rayner, Nigel W. and Robertson, Neil and Rybin, Denis and Liu, Ching-Ti and Beckmann, Jacques S. and Willems, Sara M. and Chines, Peter S. and Jackson, Anne U. and Kang, Hyun Min and Stringham, Heather M. and Song, Kijoung and Tanaka, Toshiko and Peden, John F. and Goel, Anuj and Hicks, Andrew A. and An, Ping and Mueller-Nurasyid, Martina and Franco-Cereceda, Anders and Folkersen, Lasse and Marullo, Letizia and Jansen, Hanneke and Oldehinkel, Albertine J. and Bruinenberg, Marcel and Pankow, James S. and North, Kari E. and Forouhi, Nita G. and Loos, Ruth J. F. and Edkins, Sarah and V Varga, Tibor and Hallmans, Goeran and Oksa, Heikki and Antonella, Mulas and Nagaraja, Ramaiah and Trompet, Stella and Ford, Ian and Bakker, Stephan J. L. and Kong, Augustine and Kumari, Meena and Gigante, Bruna and Herder, Christian and Munroe, Patricia B. and Caulfield, Mark and Antti, Jula and Mangino, Massimo and Small, Kerrin and Miljkovic, Iva and Liu, Yongmei and Atalay, Mustafa and Kiess, Wieland and James, Alan L. and Rivadeneira, Fernando and Uitterlinden, Andre G. and Palmer, Colin N. A. and Doney, Alex S. F. and Willemsen, Gonneke and Smit, Johannes H. and Campbell, Susan and Polasek, Ozren and Bonnycastle, Lori L. and Hercberg, Serge and Dimitriou, Maria and Bolton, Jennifer L. and Fowkes, Gerard R. and Kovacs, Peter and Lindstrom, Jaana and Zemunik, Tatijana and Bandinelli, Stefania and Wild, Sarah H. and Basart, Hanneke V. and Rathmann, Wolfgang and Grallert, Harald and Maerz, Winfried and Kleber, Marcus E. and Boehm, Bernhard O. and Peters, Annette and Pramstaller, Peter P. and Province, Michael A. and Borecki, Ingrid B. and Hastie, Nicholas D. and Rudan, Igor and Campbell, Harry and Watkins, Hugh and Farrall, Martin and Stumvoll, Michael and Ferrucci, Luigi and Waterworth, Dawn M. and Bergman, Richard N. and Collins, Francis S. and Tuomilehto, Jaakko and Watanabe, Richard M. and de Geus, Eco J. C. and Penninx, Brenda W. and Hofman, Albert and Oostra, Ben A. and Psaty, Bruce M. and Vollenweider, Peter and Wilson, James F. and Wright, Alan F. and Hovingh, G. Kees and Metspalu, Andres and Uusitupa, Matti and Magnusson, Patrik K. E. and Kyvik, Kirsten O. and Kaprio, Jaakko and Price, Jackie F. and Dedoussis, George V. and Deloukas, Panos and Meneton, Pierre and Lind, Lars and Boehnke, Michael and Shuldiner, Alan R. and van Duijn, Cornelia M. and Morris, Andrew D. and Toenjes, Anke and Peyser, Patricia A. and Beilby, John P. and Koerner, Antje and Kuusisto, Johanna and Laakso, Markku and Bornstein, Stefan R. and Schwarz, Peter E. H. and Lakka, Timo A. and Rauramaa, Rainer and Adair, Linda S. and Smith, George Davey and Spector, Tim D. and Illig, Thomas and de Faire, Ulf and Hamsten, Anders and Gudnason, Vilmundur and Kivimaki, Mika and Hingorani, Aroon and Keinanen-Kiukaanniemi, Sirkka M. and Saaristo, Timo E. and Boomsma, Dorret I. and Stefansson, Kari and van der Harst, Pim and Dupuis, Josee and Pedersen, Nancy L. and Sattar, Naveed and Harris, Tamara B. and Cucca, Francesco and Ripatti, Samuli and Salomaa, Veikko and Mohlke, Karen L. and Balkau, Beverley and Froguel, Philippe and Pouta, Anneli and Jarvelin, Marjo-Riitta and Wareham, Nicholas J. and Bouatia-Naji, Nabila and McCarthy, Mark I. and Franks, Paul and Meigs, James B. and Teslovich, Tanya M. and Florez, Jose C. and Langenberg, Claudia and Ingelsson, Erik and Prokopenko, Inga and Barroso, Ines},
  issn         = {1546-1718},
  language     = {eng},
  number       = {9},
  pages        = {991--991},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways},
  url          = {http://dx.doi.org/10.1038/ng.2385},
  volume       = {44},
  year         = {2012},
}