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

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.
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DOI:
10.1038/ng.2385
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发表时间:
2012-09
期刊:
影响因子:
30.8
通讯作者:
Barroso, Ines
Barroso, Ines
中科院分区:
生物学1区
文献类型:
--
作者:
Scott, Robert A.;Lagou, Vasiliki;Welch, Ryan P.;Wheeler, Eleanor;Montasser, May E.;Luan, Jian'an;Maegi, 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.;St Pourcain, Beate;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;Mueller-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, Goeran;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;Liu, Yongmei;Atalay, Mustafa;Kiess, Wieland;James, Alan L.;Rivadeneira, Fernando;Uitterlinden, Andre G.;Palmer, Colin N. A.;Doney, Alex S. F.;Willemsen, Gonneke;Smit, Johannes H.;Campbell, Susan;Polasek, Ozren;Bonnycastle, Lori L.;Hercberg, Serge;Dimitriou, Maria;Bolton, Jennifer L.;Fowkes, Gerard R.;Kovacs, Peter;Lindstrom, Jaana;Zemunik, Tatijana;Bandinelli, Stefania;Wild, Sarah H.;Basart, Hanneke V.;Rathmann, Wolfgang;Grallert, Harald;Maerz, Winfried;Kleber, Marcus E.;Boehm, Bernhard O.;Peters, Annette;Pramstaller, Peter P.;Province, Michael A.;Borecki, Ingrid B.;Hastie, Nicholas D.;Rudan, Igor;Campbell, Harry;Watkins, Hugh;Farrall, Martin;Stumvoll, Michael;Ferrucci, Luigi;Waterworth, Dawn M.;Bergman, Richard N.;Collins, Francis S.;Tuomilehto, Jaakko;Watanabe, Richard M.;de Geus, Eco J. C.;Penninx, Brenda W.;Hofman, Albert;Oostra, Ben A.;Psaty, Bruce M.;Vollenweider, Peter;Wilson, James F.;Wright, Alan F.;Hovingh, G. Kees;Metspalu, Andres;Uusitupa, Matti;Magnusson, Patrik K. E.;Kyvik, Kirsten O.;Kaprio, Jaakko;Price, Jackie F.;Dedoussis, George V.;Deloukas, Panos;Meneton, Pierre;Lind, Lars;Boehnke, Michael;Shuldiner, Alan R.;van Duijn, Cornelia M.;Morris, Andrew D.;Toenjes, Anke;Peyser, Patricia A.;Beilby, John P.;Koerner, Antje;Kuusisto, Johanna;Laakso, Markku;Bornstein, Stefan R.;Schwarz, Peter E. H.;Lakka, Timo A.;Rauramaa, Rainer;Adair, Linda S.;Smith, George Davey;Spector, Tim D.;Illig, Thomas;de Faire, Ulf;Hamsten, Anders;Gudnason, Vilmundur;Kivimaki, Mika;Hingorani, Aroon;Keinanen-Kiukaanniemi, Sirkka M.;Saaristo, Timo E.;Boomsma, Dorret I.;Stefansson, Kari;van der Harst, Pim;Dupuis, Josee;Pedersen, Nancy L.;Sattar, Naveed;Harris, Tamara B.;Cucca, Francesco;Ripatti, Samuli;Salomaa, Veikko;Mohlke, Karen L.;Balkau, Beverley;Froguel, Philippe;Pouta, Anneli;Jarvelin, Marjo-Riitta;Wareham, Nicholas J.;Bouatia-Naji, Nabila;McCarthy, Mark I.;Franks, Paul W.;Meigs, James B.;Teslovich, Tanya M.;Florez, Jose C.;Langenberg, Claudia;Ingelsson, Erik;Prokopenko, Inga;Barroso, Ines

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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 raised 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 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 follow-up of these newly discovered loci will further improve our understanding of glycemic control.
Klotho的功能性“ KL-VS”变体与5028英国高加索人的2型糖尿病无关。
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