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

Citation

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, et al. (2012). Large-Scale Association Analyses Identify New Loci Influencing Glycemic Traits and Provide Insight into the Underlying Biological Pathways. Nature Genetics, 44(9), 991-1005. PMCID: PMC3433394

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.

URL

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

Reference Type

Journal Article

Year Published

2012

Journal Title

Nature Genetics

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.
St. Pourcain, Beate
Wu, Ying
Andrews, Jeanette S.
Hui, Jennie
Bielak, Lawrence F.
Zhao, Wei
Horikoshi, Momoko
Navarro, Pau
Isaacs, Aaron J.
O'Connell, Jeffrey R.
Stirrups, Kathleen E.
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 R.
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 J.
Antti, Jula
Mangino, Massimo
Small, Kerrin S.
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
DIAGRAM Consortium,
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. J. H. 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
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
Korner, Antje
Kuusisto, Johanna
Laakso, Markku
Bornstein, Stefan R.
Schwarz, Peter E. H.
Lakka, Timo A.
Rauramaa, Rainer
Adair, Linda S.
Smith, George Davey
Spector, Timothy D.
Illig, Thomas
de Faire, Ulf
Hamsten, Anders
Gudnason, Vilmundur G.
Kivimaki, Mika
Hingorani, Aroon D.
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

PMCID

PMC3433394