Large-Scale Association Analyses Identify New Loci Influencing Glycemic Traits and Provide Insight into the Underlying Biological Pathways

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Journal Article

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Author(s):
Scott, Robert A.
Lagou, Vasiliki
Welch, Ryan P.
Wheeler, Eleanor
Montasser, May E.
Luan, Jian'an
Magi, Reedik
Strawbridge, Rona J.
Rehnberg, Emil
Gustafsson, Stefan
Kanoni, Stavroula
Rasmussen-Torvik, Laura J.
Yengo, Loic
Lecoeur, Cecile
Shungin, Dmitry
Sanna, Serena
Sidore, Carlo
Johnson, Paul C. D.
Jukema, J. Wouter
Johnson, Toby
Mahajan, Anubha
Verweij, Niek
Thorleifsson, Gudmar
Hottenga, Jouke-Jan
Shah, Sonia
Smith, Albert V.
Sennblad, Bengt
Gieger, Christian
Salo, Perttu
Perola, Markus
Timpson, Nicholas J.
Evans, David M.
Pourcain, Beate St.
Wu, Ying
Andrews, Jeanette S.
Hui, Jennie
Bielak, Lawrence F
Zhao, Wei
Horikoshi, Momoko
Navarro, Pau
Isaacs, Aaron
O'Connell, Jeffrey R.
Stirrups, Kathleen
Vitart, Veronique
Hayward, Caroline
Esko, Tonu
Mihailov, Evelin
Fraser, Ross M.
Fall, Tove
Voight, Benjamin F.
Raychaudhuri, Soumya
Chen, Han
Lindgren, Cecilia M.
Morris, Andrew P.
Rayner, Nigel W.
Robertson, Neil
Rybin, Denis
Liu, Ching-Ti
Beckmann, Jacques S.
Willems, Sara M.
Chines, Peter S.
Jackson, Anne U.
Kang, Hyun Min
Stringham, Heather M.
Song, Kijoung
Tanaka, Toshiko
Peden, John F.
Goel, Anuj
Hicks, Andrew A.
An, Ping
Muller-Nurasyid, Martina
Franco-Cereceda, Anders
Folkersen, Lasse
Marullo, Letizia
Jansen, Hanneke
Oldehinkel, Albertine J.
Bruinenberg, Marcel
Pankow, James S.
North, Kari E.
Forouhi, Nita G.
Loos, Ruth J. F.
Edkins, Sarah
Varga, Tibor V.
Hallmans, Goran
Oksa, Heikki
Antonella, Mulas
Nagaraja, Ramaiah
Trompet, Stella
Ford, Ian
Bakker, Stephan J. L.
Kong, Augustine
Kumari, Meena
Gigante, Bruna
Herder, Christian
Munroe, Patricia B.
Caulfield, Mark
Antti, Jula
Mangino, Massimo
Small, Kerrin
Miljkovic, Iva, et al.

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Forthcoming

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Journal Name:
Nature Genetics

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DOI:
10.1038/ng.2385

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Reference ID:
5445

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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 significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

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http://dx.doi.org/10.1038/ng.2385

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Scott, Robert A.; Lagou, Vasiliki; Welch, Ryan P.; Wheeler, Eleanor; Montasser, May E.; Luan, Jian'an; Magi, Reedik; Strawbridge, Rona J.; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J.; Yengo, Loic; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C. D.; Jukema, J. Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V.; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J.; Evans, David M.; Pourcain, Beate St.; Wu, Ying; Andrews, Jeanette S.; Hui, Jennie; Bielak, Lawrence F; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O'Connell, Jeffrey R.; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tonu; Mihailov, Evelin; Fraser, Ross M.; Fall, Tove; Voight, Benjamin F.; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M.; Morris, Andrew P.; Rayner, Nigel W.; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S.; Willems, Sara M.; Chines, Peter S.; Jackson, Anne U.; Kang, Hyun Min; Stringham, Heather M.; Song, Kijoung; Tanaka, Toshiko; Peden, John F.; Goel, Anuj; Hicks, Andrew A.; An, Ping; Muller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J.; Bruinenberg, Marcel; Pankow, James S.; North, Kari E.; Forouhi, Nita G.; Loos, Ruth J. F.; Edkins, Sarah; Varga, Tibor V.; Hallmans, Goran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J. L.; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B.; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; & Miljkovic, Iva, et al. (Forthcoming). Large-Scale Association Analyses Identify New Loci Influencing Glycemic Traits and Provide Insight into the Underlying Biological Pathways. Nature Genetics.