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

Robert A. Scott; Vasiliki Lagou; Ryan P. Welch; Eleanor Wheeler; May E. Montasser; Jian'An Luan; Reedik MäGi; Rona J. Strawbridge; Emil Rehnberg; Stefan Gustafsson; Stavroula Kanoni; Laura J. Rasmussen-Torvik; Loïc Yengo; Cecile Lecoeur; Dmitry Shungin; Serena Sanna; Carlo Sidore; Paul C.D. Johnson; J. Wouter Jukema; Toby Johnson; Anubha Mahajan; Niek Verweij; Gudmar Thorleifsson; Jouke Jan Hottenga; Sonia Shah; Albert V. Smith; Bengt Sennblad; Christian Gieger; Perttu Salo; Markus Perola; Nicholas J. Timpson; David M. Evans; Beate St Pourcain; Ying Wu; Jeanette S. Andrews; Jennie Hui; Lawrence F. Bielak; Wei Zhao; Momoko Horikoshi; Pau Navarro; Aaron Isaacs; Jeffrey R. O'Connell; Kathleen Stirrups; Veronique Vitart; Caroline Hayward; Tõnu Esko; Evelin Mihailov; Ross M. Fraser; Tove Fall; Benjamin F. Voight; Soumya Raychaudhuri; Han Chen; Cecilia M. Lindgren; Andrew P. Morris; Nigel W. Rayner; Neil Robertson; Denis Rybin; Ching Ti Liu; Jacques S. Beckmann; Sara M. Willems; Peter S. Chines; Anne U. Jackson; Hyun Min Kang; Heather M. Stringham; Kijoung Song; Toshiko Tanaka; John F. Peden; Anuj Goel; Andrew A. Hicks; Ping An; Martina MüLler-Nurasyid; Anders Franco-Cereceda; Lasse Folkersen; Letizia Marullo; Hanneke Jansen; Albertine J. Oldehinkel; Marcel Bruinenberg; James S. Pankow; Kari E. North; Nita G. Forouhi; Ruth J.F. Loos; Sarah Edkins; Tibor V. Varga; Göran Hallmans; Heikki Oksa; Mulas Antonella; Ramaiah Nagaraja; Stella Trompet; Ian Ford; Stephan J.L. Bakker; Augustine Kong; Meena Kumari; Bruna Gigante; Christian Herder; Patricia B. Munroe; Mark Caulfield; Jula Antti; Massimo Mangino; Kerrin Small; Iva Miljkovic; Yongmei Liu; Mustafa Atalay; Wieland Kiess; Alan L. James; Fernando Rivadeneira; Andre G. Uitterlinden; Colin N.A. Palmer; Alex S.F. Doney; Gonneke Willemsen; Johannes H. Smit; Susan Campbell; Ozren Polasek; Lori L. Bonnycastle; Serge Hercberg; Maria Dimitriou; Jennifer L. Bolton; Gerard R. Fowkes; Peter Kovacs; Jaana LindströM; Tatijana Zemunik; Stefania Bandinelli; Sarah H. Wild; Hanneke V. Basart; Wolfgang Rathmann; Harald Grallert; Winfried Maerz; Marcus E. Kleber; Bernhard O. Boehm; Annette Peters; Peter P. Pramstaller; Michael A. Province; Ingrid B. Borecki; Nicholas D. Hastie; Igor Rudan; Harry Campbell; Hugh Watkins; Martin Farrall; Michael Stumvoll; Luigi Ferrucci; Dawn M. Waterworth; Richard N. Bergman; Francis S. Collins; Jaakko Tuomilehto; Richard M. Watanabe; Eco J.C. De Geus; Brenda W. Penninx; Albert Hofman; Ben A. Oostra; Bruce M. Psaty; Peter Vollenweider; James F. Wilson; Alan F. Wright; G. Kees Hovingh; Andres Metspalu; Matti Uusitupa; Patrik K.E. Magnusson; Kirsten O. Kyvik; Jaakko Kaprio; Jackie F. Price; George V. Dedoussis; Panos Deloukas; Pierre Meneton; Lars Lind; Michael Boehnke; Alan R. Shuldiner; Cornelia M. Van Duijn; Andrew D. Morris; Anke Toenjes; Patricia A. Peyser; John P. Beilby; Antje KöRner; Johanna Kuusisto; Markku Laakso; Stefan R. Bornstein; Peter E.H. Schwarz; Timo A. Lakka; Rainer Rauramaa; Linda S. Adair; George Davey Smith; Tim D. Spector; Thomas Illig; Ulf De Faire; Anders Hamsten; Vilmundur Gudnason; Mika Kivimaki; Aroon Hingorani; Sirkka M. Keinanen-Kiukaanniemi; Timo E. Saaristo; Dorret I. Boomsma; Kari Stefansson; Pim Van Der Harst; Josée Dupuis; Nancy L. Pedersen; Naveed Sattar; Tamara B. Harris; Francesco Cucca; Samuli Ripatti; Veikko Salomaa; Karen L. Mohlke; Beverley Balkau; Philippe Froguel; Anneli Pouta; Marjo Riitta Jarvelin; Nicholas J. Wareham; Nabila Bouatia-Naji; Mark I. McCarthy; Paul W. Franks; James B. Meigs; Tanya M. Teslovich; Jose C. Florez; Claudia Langenberg; Erik Ingelsson; Inga Prokopenko; Iněs Barroso

doi:10.1038/ng.2385

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

Robert A. Scott, Vasiliki Lagou, Ryan P. Welch, Eleanor Wheeler, May E. Montasser, Jian'An Luan, Reedik MäGi, Rona J. Strawbridge, Emil Rehnberg, Stefan Gustafsson, Stavroula Kanoni, Laura J. Rasmussen-Torvik, Loïc Yengo, Cecile Lecoeur, Dmitry Shungin, Serena Sanna, Carlo Sidore, Paul C.D. Johnson, J. Wouter Jukema, Toby JohnsonAnubha Mahajan, Niek Verweij, Gudmar Thorleifsson, Jouke Jan Hottenga, Sonia Shah, Albert V. Smith, Bengt Sennblad, Christian Gieger, Perttu Salo, Markus Perola, Nicholas J. Timpson, David M. Evans, Beate St Pourcain, Ying Wu, Jeanette S. Andrews, Jennie Hui, Lawrence F. Bielak, Wei Zhao, Momoko Horikoshi, Pau Navarro, Aaron Isaacs, Jeffrey R. O'Connell, Kathleen Stirrups, Veronique Vitart, Caroline Hayward, Tõnu Esko, Evelin Mihailov, Ross M. Fraser, Tove Fall, Benjamin F. Voight, Soumya Raychaudhuri, Han Chen, Cecilia M. Lindgren, Andrew P. Morris, Nigel W. Rayner, Neil Robertson, Denis Rybin, Ching Ti Liu, Jacques S. Beckmann, Sara M. Willems, Peter S. Chines, Anne U. Jackson, Hyun Min Kang, Heather M. Stringham, Kijoung Song, Toshiko Tanaka, John F. Peden, Anuj Goel, Andrew A. Hicks, Ping An, Martina MüLler-Nurasyid, Anders Franco-Cereceda, Lasse Folkersen, Letizia Marullo, Hanneke Jansen, Albertine J. Oldehinkel, Marcel Bruinenberg, James S. Pankow, Kari E. North, Nita G. Forouhi, Ruth J.F. Loos, Sarah Edkins, Tibor V. Varga, Göran Hallmans, Heikki Oksa, Mulas Antonella, Ramaiah Nagaraja, Stella Trompet, Ian Ford, Stephan J.L. Bakker, Augustine Kong, Meena Kumari, Bruna Gigante, Christian Herder, Patricia B. Munroe, Mark Caulfield, Jula Antti, Massimo Mangino, Kerrin Small, Iva Miljkovic, Yongmei Liu, Mustafa Atalay, Wieland Kiess, Alan L. James, Fernando Rivadeneira, Andre G. Uitterlinden, Colin N.A. Palmer, Alex S.F. Doney, Gonneke Willemsen, Johannes H. Smit, Susan Campbell, Ozren Polasek, Lori L. Bonnycastle, Serge Hercberg, Maria Dimitriou, Jennifer L. Bolton, Gerard R. Fowkes, Peter Kovacs, Jaana LindströM, Tatijana Zemunik, Stefania Bandinelli, Sarah H. Wild, Hanneke V. Basart, Wolfgang Rathmann, Harald Grallert, Winfried Maerz, Marcus E. Kleber, Bernhard O. Boehm, Annette Peters, Peter P. Pramstaller, Michael A. Province, Ingrid B. Borecki, Nicholas D. Hastie, Igor Rudan, Harry Campbell, Hugh Watkins, Martin Farrall, Michael Stumvoll, Luigi Ferrucci, Dawn M. Waterworth, Richard N. Bergman, Francis S. Collins, Jaakko Tuomilehto, Richard M. Watanabe, Eco J.C. De Geus, Brenda W. Penninx, Albert Hofman, Ben A. Oostra, Bruce M. Psaty, Peter Vollenweider, James F. Wilson, Alan F. Wright, G. Kees Hovingh, Andres Metspalu, Matti Uusitupa, Patrik K.E. Magnusson, Kirsten O. Kyvik, Jaakko Kaprio, Jackie F. Price, George V. Dedoussis, Panos Deloukas, Pierre Meneton, Lars Lind, Michael Boehnke, Alan R. Shuldiner, Cornelia M. Van Duijn, Andrew D. Morris, Anke Toenjes, Patricia A. Peyser, John P. Beilby, Antje KöRner, Johanna Kuusisto, Markku Laakso, Stefan R. Bornstein, Peter E.H. Schwarz, Timo A. Lakka, Rainer Rauramaa, Linda S. Adair, George Davey Smith, Tim D. Spector, Thomas Illig, Ulf De Faire, Anders Hamsten, Vilmundur Gudnason, Mika Kivimaki, Aroon Hingorani, Sirkka M. Keinanen-Kiukaanniemi, Timo E. Saaristo, Dorret I. Boomsma, Kari Stefansson, Pim Van Der Harst, Josée Dupuis, Nancy L. Pedersen, Naveed Sattar, Tamara B. Harris, Francesco Cucca, Samuli Ripatti, Veikko Salomaa, Karen L. Mohlke, Beverley Balkau, Philippe Froguel, Anneli Pouta, Marjo Riitta Jarvelin, Nicholas J. Wareham, Nabila Bouatia-Naji, Mark I. McCarthy, Paul W. Franks, James B. Meigs, Tanya M. Teslovich, Jose C. Florez, Claudia Langenberg, Erik Ingelsson, Inga Prokopenko, Iněs Barroso

Research output: Contribution to journal › Article › peer-review

679 Scopus citations

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.

Original language	English
Pages (from-to)	991-1005
Number of pages	15
Journal	Nature Genetics
Volume	44
Issue number	9
DOIs	https://doi.org/10.1038/ng.2385
State	Published - Sep 2012

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10.1038/ng.2385

Cite this

Scott, R. A., Lagou, V., Welch, R. P., Wheeler, E., Montasser, M. E., Luan, JA., MäGi, R., Strawbridge, R. J., Rehnberg, E., Gustafsson, S., Kanoni, S., Rasmussen-Torvik, L. J., Yengo, L., Lecoeur, C., Shungin, D., Sanna, S., Sidore, C., Johnson, P. C. D., Jukema, J. W., ... Barroso, I. (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. https://doi.org/10.1038/ng.2385

@article{4dc60fbc62fd48a6a6ede6166382ff1a,

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

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.",

author = "Scott, {Robert A.} and Vasiliki Lagou and Welch, {Ryan P.} and Eleanor Wheeler and Montasser, {May E.} and Jian'An Luan and Reedik M{\"a}Gi and Strawbridge, {Rona J.} and Emil Rehnberg and Stefan Gustafsson and Stavroula Kanoni and Rasmussen-Torvik, {Laura J.} and Lo{\"i}c Yengo and Cecile Lecoeur and Dmitry Shungin and Serena Sanna and Carlo Sidore and Johnson, {Paul C.D.} and Jukema, {J. Wouter} and Toby Johnson and Anubha Mahajan and Niek Verweij and Gudmar Thorleifsson and Hottenga, {Jouke Jan} and Sonia Shah and Smith, {Albert V.} and Bengt Sennblad and Christian Gieger and Perttu Salo and Markus Perola and Timpson, {Nicholas J.} and Evans, {David M.} and Pourcain, {Beate St} and Ying Wu and Andrews, {Jeanette S.} and Jennie Hui and Bielak, {Lawrence F.} and Wei Zhao and Momoko Horikoshi and Pau Navarro and Aaron Isaacs and O'Connell, {Jeffrey R.} and Kathleen Stirrups and Veronique Vitart and Caroline Hayward and T{\~o}nu Esko and Evelin Mihailov and Fraser, {Ross M.} and Tove Fall and Voight, {Benjamin F.} and Soumya Raychaudhuri and Han Chen and Lindgren, {Cecilia M.} and Morris, {Andrew P.} and Rayner, {Nigel W.} and Neil Robertson and Denis Rybin 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 Kijoung Song and Toshiko Tanaka and Peden, {John F.} and Anuj Goel and Hicks, {Andrew A.} and Ping An and Martina M{\"u}Ller-Nurasyid and Anders Franco-Cereceda and Lasse Folkersen and Letizia Marullo and Hanneke Jansen and Oldehinkel, {Albertine J.} and Marcel Bruinenberg and Pankow, {James S.} and North, {Kari E.} and Forouhi, {Nita G.} and Loos, {Ruth J.F.} and Sarah Edkins and Varga, {Tibor V.} and G{\"o}ran Hallmans and Heikki Oksa and Mulas Antonella and Ramaiah Nagaraja and Stella Trompet and Ian Ford and Bakker, {Stephan J.L.} and Augustine Kong and Meena Kumari and Bruna Gigante and Christian Herder and Munroe, {Patricia B.} and Mark Caulfield and Jula Antti and Massimo Mangino and Kerrin Small and Iva Miljkovic and Yongmei Liu and Mustafa Atalay and Wieland Kiess and James, {Alan L.} and Fernando Rivadeneira and Uitterlinden, {Andre G.} and Palmer, {Colin N.A.} and Doney, {Alex S.F.} and Gonneke Willemsen and Smit, {Johannes H.} and Susan Campbell and Ozren Polasek and Bonnycastle, {Lori L.} and Serge Hercberg and Maria Dimitriou and Bolton, {Jennifer L.} and Fowkes, {Gerard R.} and Peter Kovacs and Jaana Lindstr{\"o}M and Tatijana Zemunik and Stefania Bandinelli and Wild, {Sarah H.} and Basart, {Hanneke V.} and Wolfgang Rathmann and Harald Grallert and Winfried Maerz and Kleber, {Marcus E.} and Boehm, {Bernhard O.} and Annette Peters and Pramstaller, {Peter P.} and Province, {Michael A.} and Borecki, {Ingrid B.} and Hastie, {Nicholas D.} and Igor Rudan and Harry Campbell and Hugh Watkins and Martin Farrall and Michael Stumvoll and Luigi Ferrucci and Waterworth, {Dawn M.} and Bergman, {Richard N.} and Collins, {Francis S.} and Jaakko Tuomilehto and Watanabe, {Richard M.} and {De Geus}, {Eco J.C.} and Penninx, {Brenda W.} and Albert Hofman and Oostra, {Ben A.} and Psaty, {Bruce M.} and Peter Vollenweider and Wilson, {James F.} and Wright, {Alan F.} and Hovingh, {G. Kees} and Andres Metspalu and Matti Uusitupa and Magnusson, {Patrik K.E.} and Kyvik, {Kirsten O.} and Jaakko Kaprio and Price, {Jackie F.} and Dedoussis, {George V.} and Panos Deloukas and Pierre Meneton and Lars Lind and Michael Boehnke and Shuldiner, {Alan R.} and {Van Duijn}, {Cornelia M.} and Morris, {Andrew D.} and Anke Toenjes and Peyser, {Patricia A.} and Beilby, {John P.} and Antje K{\"o}Rner and Johanna Kuusisto and Markku Laakso and Bornstein, {Stefan R.} and Schwarz, {Peter E.H.} and Lakka, {Timo A.} and Rainer Rauramaa and Adair, {Linda S.} and Smith, {George Davey} and Spector, {Tim D.} and Thomas Illig and Faire, {Ulf De} and Anders Hamsten and Vilmundur Gudnason and Mika Kivimaki and Aroon Hingorani and Keinanen-Kiukaanniemi, {Sirkka M.} and Saaristo, {Timo E.} and Boomsma, {Dorret I.} and Kari Stefansson and {Van Der Harst}, Pim and Jos{\'e}e Dupuis and Pedersen, {Nancy L.} and Naveed Sattar and Harris, {Tamara B.} and Francesco Cucca and Samuli Ripatti and Veikko Salomaa and Mohlke, {Karen L.} and Beverley Balkau and Philippe Froguel and Anneli Pouta and Jarvelin, {Marjo Riitta} and Wareham, {Nicholas J.} and Nabila Bouatia-Naji and McCarthy, {Mark I.} and Franks, {Paul W.} and Meigs, {James B.} and Teslovich, {Tanya M.} and Florez, {Jose C.} and Claudia Langenberg and Erik Ingelsson and Inga Prokopenko and In{\v e}s Barroso",

year = "2012",

month = sep,

doi = "10.1038/ng.2385",

language = "English",

volume = "44",

pages = "991--1005",

journal = "Nature Genetics",

issn = "1061-4036",

number = "9",

}

Scott, RA, Lagou, V, Welch, RP, Wheeler, E, Montasser, ME, Luan, JA, MäGi, R, Strawbridge, RJ, Rehnberg, E, Gustafsson, S, Kanoni, S, Rasmussen-Torvik, LJ, Yengo, L, Lecoeur, C, Shungin, D, Sanna, S, Sidore, C, Johnson, PCD, Jukema, JW, Johnson, T, Mahajan, A, Verweij, N, Thorleifsson, G, Hottenga, JJ, Shah, S, Smith, AV, Sennblad, B, Gieger, C, Salo, P, Perola, M, Timpson, NJ, Evans, DM, Pourcain, BS, Wu, Y, Andrews, JS, Hui, J, Bielak, LF, Zhao, W, Horikoshi, M, Navarro, P, Isaacs, A, O'Connell, JR, Stirrups, K, Vitart, V, Hayward, C, Esko, T, Mihailov, E, Fraser, RM, Fall, T, Voight, BF, Raychaudhuri, S, Chen, H, Lindgren, CM, Morris, AP, Rayner, NW, Robertson, N, Rybin, D, Liu, CT, Beckmann, JS, Willems, SM, Chines, PS, Jackson, AU, Kang, HM, Stringham, HM, Song, K, Tanaka, T, Peden, JF, Goel, A, Hicks, AA, An, P, MüLler-Nurasyid, M, Franco-Cereceda, A, Folkersen, L, Marullo, L, Jansen, H, Oldehinkel, AJ, Bruinenberg, M, Pankow, JS, North, KE, Forouhi, NG, Loos, RJF, Edkins, S, Varga, TV, Hallmans, G, Oksa, H, Antonella, M, Nagaraja, R, Trompet, S, Ford, I, Bakker, SJL, Kong, A, Kumari, M, Gigante, B, Herder, C, Munroe, PB, Caulfield, M, Antti, J, Mangino, M, Small, K, Miljkovic, I, Liu, Y, Atalay, M, Kiess, W, James, AL, Rivadeneira, F, Uitterlinden, AG, Palmer, CNA, Doney, ASF, Willemsen, G, Smit, JH, Campbell, S, Polasek, O, Bonnycastle, LL, Hercberg, S, Dimitriou, M, Bolton, JL, Fowkes, GR, Kovacs, P, LindströM, J, Zemunik, T, Bandinelli, S, Wild, SH, Basart, HV, Rathmann, W, Grallert, H, Maerz, W, Kleber, ME, Boehm, BO, Peters, A, Pramstaller, PP, Province, MA, Borecki, IB, Hastie, ND, Rudan, I, Campbell, H, Watkins, H, Farrall, M, Stumvoll, M, Ferrucci, L, Waterworth, DM, Bergman, RN, Collins, FS, Tuomilehto, J, Watanabe, RM, De Geus, EJC, Penninx, BW, Hofman, A, Oostra, BA, Psaty, BM, Vollenweider, P, Wilson, JF, Wright, AF, Hovingh, GK, Metspalu, A, Uusitupa, M, Magnusson, PKE, Kyvik, KO, Kaprio, J, Price, JF, Dedoussis, GV, Deloukas, P, Meneton, P, Lind, L, Boehnke, M, Shuldiner, AR, Van Duijn, CM, Morris, AD, Toenjes, A, Peyser, PA, Beilby, JP, KöRner, A, Kuusisto, J, Laakso, M, Bornstein, SR, Schwarz, PEH, Lakka, TA, Rauramaa, R, Adair, LS, Smith, GD, Spector, TD, Illig, T, Faire, UD, Hamsten, A, Gudnason, V, Kivimaki, M, Hingorani, A, Keinanen-Kiukaanniemi, SM, Saaristo, TE, Boomsma, DI, Stefansson, K, Van Der Harst, P, Dupuis, J, Pedersen, NL, Sattar, N, Harris, TB, Cucca, F, Ripatti, S, Salomaa, V, Mohlke, KL, Balkau, B, Froguel, P, Pouta, A, Jarvelin, MR, Wareham, NJ, Bouatia-Naji, N, McCarthy, MI, Franks, PW, Meigs, JB, Teslovich, TM, Florez, JC, Langenberg, C, Ingelsson, E, Prokopenko, I & Barroso, I 2012, 'Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways', Nature Genetics, vol. 44, no. 9, pp. 991-1005. https://doi.org/10.1038/ng.2385

TY - JOUR

T1 - Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

AU - Scott, Robert A.

AU - Lagou, Vasiliki

AU - Welch, Ryan P.

AU - Wheeler, Eleanor

AU - Montasser, May E.

AU - Luan, Jian'An

AU - MäGi, Reedik

AU - Strawbridge, Rona J.

AU - Rehnberg, Emil

AU - Gustafsson, Stefan

AU - Kanoni, Stavroula

AU - Rasmussen-Torvik, Laura J.

AU - Yengo, Loïc

AU - Lecoeur, Cecile

AU - Shungin, Dmitry

AU - Sanna, Serena

AU - Sidore, Carlo

AU - Johnson, Paul C.D.

AU - Jukema, J. Wouter

AU - Johnson, Toby

AU - Mahajan, Anubha

AU - Verweij, Niek

AU - Thorleifsson, Gudmar

AU - Hottenga, Jouke Jan

AU - Shah, Sonia

AU - Smith, Albert V.

AU - Sennblad, Bengt

AU - Gieger, Christian

AU - Salo, Perttu

AU - Perola, Markus

AU - Timpson, Nicholas J.

AU - Evans, David M.

AU - Pourcain, Beate St

AU - Wu, Ying

AU - Andrews, Jeanette S.

AU - Hui, Jennie

AU - Bielak, Lawrence F.

AU - Zhao, Wei

AU - Horikoshi, Momoko

AU - Navarro, Pau

AU - Isaacs, Aaron

AU - O'Connell, Jeffrey R.

AU - Stirrups, Kathleen

AU - Vitart, Veronique

AU - Hayward, Caroline

AU - Esko, Tõnu

AU - Mihailov, Evelin

AU - Fraser, Ross M.

AU - Fall, Tove

AU - Voight, Benjamin F.

AU - Raychaudhuri, Soumya

AU - Chen, Han

AU - Lindgren, Cecilia M.

AU - Morris, Andrew P.

AU - Rayner, Nigel W.

AU - Robertson, Neil

AU - Rybin, Denis

AU - Liu, Ching Ti

AU - Beckmann, Jacques S.

AU - Willems, Sara M.

AU - Chines, Peter S.

AU - Jackson, Anne U.

AU - Kang, Hyun Min

AU - Stringham, Heather M.

AU - Song, Kijoung

AU - Tanaka, Toshiko

AU - Peden, John F.

AU - Goel, Anuj

AU - Hicks, Andrew A.

AU - An, Ping

AU - MüLler-Nurasyid, Martina

AU - Franco-Cereceda, Anders

AU - Folkersen, Lasse

AU - Marullo, Letizia

AU - Jansen, Hanneke

AU - Oldehinkel, Albertine J.

AU - Bruinenberg, Marcel

AU - Pankow, James S.

AU - North, Kari E.

AU - Forouhi, Nita G.

AU - Loos, Ruth J.F.

AU - Edkins, Sarah

AU - Varga, Tibor V.

AU - Hallmans, Göran

AU - Oksa, Heikki

AU - Antonella, Mulas

AU - Nagaraja, Ramaiah

AU - Trompet, Stella

AU - Ford, Ian

AU - Bakker, Stephan J.L.

AU - Kong, Augustine

AU - Kumari, Meena

AU - Gigante, Bruna

AU - Herder, Christian

AU - Munroe, Patricia B.

AU - Caulfield, Mark

AU - Antti, Jula

AU - Mangino, Massimo

AU - Small, Kerrin

AU - Miljkovic, Iva

AU - Liu, Yongmei

AU - Atalay, Mustafa

AU - Kiess, Wieland

AU - James, Alan L.

AU - Rivadeneira, Fernando

AU - Uitterlinden, Andre G.

AU - Palmer, Colin N.A.

AU - Doney, Alex S.F.

AU - Willemsen, Gonneke

AU - Smit, Johannes H.

AU - Campbell, Susan

AU - Polasek, Ozren

AU - Bonnycastle, Lori L.

AU - Hercberg, Serge

AU - Dimitriou, Maria

AU - Bolton, Jennifer L.

AU - Fowkes, Gerard R.

AU - Kovacs, Peter

AU - LindströM, Jaana

AU - Zemunik, Tatijana

AU - Bandinelli, Stefania

AU - Wild, Sarah H.

AU - Basart, Hanneke V.

AU - Rathmann, Wolfgang

AU - Grallert, Harald

AU - Maerz, Winfried

AU - Kleber, Marcus E.

AU - Boehm, Bernhard O.

AU - Peters, Annette

AU - Pramstaller, Peter P.

AU - Province, Michael A.

AU - Borecki, Ingrid B.

AU - Hastie, Nicholas D.

AU - Rudan, Igor

AU - Campbell, Harry

AU - Watkins, Hugh

AU - Farrall, Martin

AU - Stumvoll, Michael

AU - Ferrucci, Luigi

AU - Waterworth, Dawn M.

AU - Bergman, Richard N.

AU - Collins, Francis S.

AU - Tuomilehto, Jaakko

AU - Watanabe, Richard M.

AU - De Geus, Eco J.C.

AU - Penninx, Brenda W.

AU - Hofman, Albert

AU - Oostra, Ben A.

AU - Psaty, Bruce M.

AU - Vollenweider, Peter

AU - Wilson, James F.

AU - Wright, Alan F.

AU - Hovingh, G. Kees

AU - Metspalu, Andres

AU - Uusitupa, Matti

AU - Magnusson, Patrik K.E.

AU - Kyvik, Kirsten O.

AU - Kaprio, Jaakko

AU - Price, Jackie F.

AU - Dedoussis, George V.

AU - Deloukas, Panos

AU - Meneton, Pierre

AU - Lind, Lars

AU - Boehnke, Michael

AU - Shuldiner, Alan R.

AU - Van Duijn, Cornelia M.

AU - Morris, Andrew D.

AU - Toenjes, Anke

AU - Peyser, Patricia A.

AU - Beilby, John P.

AU - KöRner, Antje

AU - Kuusisto, Johanna

AU - Laakso, Markku

AU - Bornstein, Stefan R.

AU - Schwarz, Peter E.H.

AU - Lakka, Timo A.

AU - Rauramaa, Rainer

AU - Adair, Linda S.

AU - Smith, George Davey

AU - Spector, Tim D.

AU - Illig, Thomas

AU - Faire, Ulf De

AU - Hamsten, Anders

AU - Gudnason, Vilmundur

AU - Kivimaki, Mika

AU - Hingorani, Aroon

AU - Keinanen-Kiukaanniemi, Sirkka M.

AU - Saaristo, Timo E.

AU - Boomsma, Dorret I.

AU - Stefansson, Kari

AU - Van Der Harst, Pim

AU - Dupuis, Josée

AU - Pedersen, Nancy L.

AU - Sattar, Naveed

AU - Harris, Tamara B.

AU - Cucca, Francesco

AU - Ripatti, Samuli

AU - Salomaa, Veikko

AU - Mohlke, Karen L.

AU - Balkau, Beverley

AU - Froguel, Philippe

AU - Pouta, Anneli

AU - Jarvelin, Marjo Riitta

AU - Wareham, Nicholas J.

AU - Bouatia-Naji, Nabila

AU - McCarthy, Mark I.

AU - Franks, Paul W.

AU - Meigs, James B.

AU - Teslovich, Tanya M.

AU - Florez, Jose C.

AU - Langenberg, Claudia

AU - Ingelsson, Erik

AU - Prokopenko, Inga

AU - Barroso, Iněs

PY - 2012/9

Y1 - 2012/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84865693929&partnerID=8YFLogxK

U2 - 10.1038/ng.2385

DO - 10.1038/ng.2385

M3 - Article

C2 - 22885924

AN - SCOPUS:84865693929

SN - 1061-4036

VL - 44

SP - 991

EP - 1005

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -

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

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