A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Muther, Consortium; Wouter Jukema, J.; Scott, Robert A.; Tönjes, Anke; Van Duijn, Cm M.; Tm, Frayling; Tb, Harris; Wh, Kao; Sl, Kardia; Yv, Sun; Toenjes, Anke; Sh, Wild; Sm, Willems; Salo, Perttu; Sattar, Naveed; Strawbridge, Rona J.; Shungin, Dmitry; van Duijn, Cornelia M.; Tanaka, Toshiko; de Andrade, Mariza; Manning, Alisa K.; Hivert, Marie-France; Grimsby, Jonna L.; Liu, Ching-Ti; Bielak, Lawrence F.; Hottenga, Jouke-Jan; Jackson, Anne U.; Bouatia-Naji, Nabila; Lahti, Jari; Lecoeur, Cecile; de Faire, Ulf; Martínez-Larrad, María Teresa; Chen, Han; Navarro, Pau; Montasser, May E.; Perry, John R. B.; Rasmussen-Torvik, Laura J.; Rybin, Denis; An, Ping; Andrews, Jeanette S.; de Geus, Eco; Aspelund, Thor; Atalay, Mustafa; Aulchenko, Yurii; Balkau, Beverley; Johnson, Toby; Bandinelli, Stefania; Beckmann, Jacques S.; Prokopenko, Inga; Beilby, John P.; Ak, Manning; Bellis, Claire; Amin, Najaf; Diagram, Consortium; Bergman, Richard N.; Blangero, John; Boban, Mladen; Ingelsson, Erik; Barnes, Daniel; Boehnke, Michael; Boerwinkle, Eric; Mt, Martinez Larrad; Cadby, Gemma; Bonnycastle, Lori Ll; Mf, Hivert; Boomsma, Dorret I.; Liu, Ym; Borecki, Ingrid B.; Me, Montasser; Böttcher, Yvonne; Bouchard, Claude; Kanoni, Stavroula; Jr, Perry; Brunner, Eric; Lj, Rasmussen Torvik; Budimir, Danijela; Ladenvall, Claes; Campbell, Harry; Carlson, Olga; Liu, Yongmei; Chines, Peter S.; Lagou, Vasiliki; Clarke, Robert; Rj, Strawbridge; Collins, Francis S.; Cm, van Duijn; Js, Andrews; Couper, David; De Andrade, M.; Dedoussis, George V.; Corbatón-Anchuelo, Arturo; Deloukas, Panos; Ra, Scott; Dimitriou, Maria; Egan, Josephine M.; Jl, Grimsby; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Js, Beckmann; Räikkönen, Katri; Eury, Elodie; Ferrucci, Luigi; Jp, Beilby; Ford, Ian; Forouhi, Nita G.; Rn, Bergman; Fox, Caroline S.; Saaristo, Timo; Sabater-Lleal, Maria; Savage, David B.; Franzosi, Maria Grazia; Salomaa, Veikko; Ll, Bonnycastle; Franks, Paul W.; Saxena, Richa; Frayling, Timothy M.; Di, Boomsma; Schwarz, Peter; Froguel, Philippe; Shuldiner, Alan R.; Galan, Pilar; Ib, Borecki; Sijbrands, Eric J. G.; Seedorf, Udo; Siscovick, David S.; Sennblad, Bengt; Gigante, Bruna; Smit, Johannes H.; Serrano-Ríos, Manuel; Glazer, Nicole L.; Small, Kerrin S.; Boettcher, Yvonne; Goel, Anuj; Smith, Nicholas L.; Groop, Leif; Smith, Albert Vernon; Gudnason, Vilmundur; Ps, Chines; Hallmans, Göran; Stančáková, Alena; Hamsten, Anders; Sun, Yan V.; Stirrups, Kathleen; Hansson, Ola; Swift, Amy J.; Stumvoll, Michael; Fs, Collins; Tönjes, Anke; Harris, Tamara B.; Hayward, Caroline; Jj, Hottenga; Tuomilehto, Jaakko; Heath, Simon; Uitterlinden, Andre G.; Trompet, Stella; Hercberg, Serge; Gv, Dedoussis; Hicks, Andrew Aa; Uusitupa, Matti; De Faire, U.; Hingorani, Aroon; Vohl, Marie-Claude; Vikström, Max; Voight, Benjamin F.; Vitart, Veronique; Hofman, Albert; Jm, Egan; Mr, Erdos; Hui, Jennie; Vollenweider, Peter; Waterworth, Dawn M.; Hung, Joseph; Waeber, Gerard; Jarvelin, Marjo-Riitta; Watkins, Hugh; Au, Jackson; Jhun, Min A.; Wheeler, Eleanor; Johnson, Paul C. D.; Wild, Sarah H.; Widen, Elisabeth; Jukema, Jw Wouter; Ng, Forouhi; Willems, Sara M.; Jula, Antti; Kao, Wh H.; Wilson, James F.; Willemsen, Gonneke; Kaprio, Jaakko; Witteman, Jacqueline C. M.; Cs, Fox; Wright, Alan F.; Keinanen-Kiukaanniemi, Sirkka; Kardia, Sharon L. R.; Yaghootkar, Hanieh; Kivimaki, Mika; Mg, Franzosi; Zelenika, Diana; Kolcic, Ivana; Zemunik, Tatijana; Kovacs, Peter; Zgaga, Lina; Pw, Franks; Wareham, Nicholas J.; Kumari, Meena; Kuusisto, Johanna; Jg, Eriksson; Watanabe, Richard M.; Ct, Liu; Kyvik, Kirsten Ohm; Laakso, Markku; Lakka, Timo; De Geus, E.; Lannfelt, Lars; Nl, Glazer; Leander, Karin; Launer, Lenore J.; Li, Guo; Lf, Bielak; Lind, Lars; Lathrop, Gm Mark; Lindström, Jaana; Lobbens, Stéphane; Luan, Jian’an; Aa, Hicks; Loos, Ruth J. F.; Lyssenko, Valeriya; Mr, Jarvelin; Marmot, Michael; Mägi, Reedik; Ma, Jhun; Meneton, Pierre; Magnusson, Patrik K. E.; Mooser, Vincent; Pc, Johnson; Jw, Jukema; Miljkovic, Iva; Mohlke, Karen L.; Morken, Mario A.; Narisu, Narisu; O'Connell, Jeff; Ko, Kyvik; Ong, Ken Kk; Palotie, Aarno; Oostra, Ben A.; Gm, Lathrop; Palmer, Lyle J.; Lj, Launer; Pehlic, Marina; Pankow, James S.; Peltonen, Leena; Penninx, Brenda W. J. H.; Peden, John F.; Rj, Loos; Pericic, Marijana; Pk, Magnusson; Pedersen, Nancy L.; Perola, Markus; Perusse, Louis; Kl, Mohlke; Polasek, Ozren; Magi, Reedik; Rauramaa, Rainer; Ma, Morken; Pramstaller, Peter Pp; Peyser, Patricia A.; Kk, Ong; Province, Michael A.; Rehnberg, Emil; Ba, Oostra; Rice, Ken; Rotter, Jerome I.; Lj, Palmer; Rudan, Igor; Ruokonen, Aimo; Mark Lathrop, G.; Js, Pankow; Jf, Peden; Nl, Pedersen; Pa, Peyser; Pp, Pramstaller; Ma, Province; Ji, Rotter; Raikkonen, Katri; Db, Savage; Ar, Shuldiner; Ej, Sijbrands; Ds, Siscovick; Böttcher, Yvonne; Jh, Smit; Ks, Small; Nl, Smith; Av, Smith; Aj, Swift; Ag, Uitterlinden; Mc, Vohl; Bf, Voight; Dm, Waterworth; Jf, Wilson; Jc, Witteman; Af, Wright; Mr, Järvelin; Geus, E. J. C.; Consortium, DIAbetes Genetics Replication And Meta-Analysis (Diagram); Mägi, Reedik; Consortium, Multiple Tissue Human Expression Resource (MUTHER); O’Connell, Jeff; Nj, Wareham; Pérusse, Louis; Mi, McCarthy; McCarthy, Mark I.; Barroso, Inês; Rm, Watanabe; Florez, Jose C.; Jc, Florez; Dupuis, Josee; Meigs, James B.; Jb, Meigs; Langenberg, Claudia; ,

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Rona J. Strawbridge
Muther et al., 2012

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@article{Muther2012,
  abstract = {Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P &lt; 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.},
  author = {Muther, Consortium and Wouter Jukema, J. and Scott, Robert A. and Tönjes, Anke and Van Duijn, Cm M. and Tm, Frayling and Tb, Harris and Wh, Kao and Sl, Kardia and Yv, Sun and Toenjes, Anke and Sh, Wild and Sm, Willems and Salo, Perttu and Sattar, Naveed and Strawbridge, Rona J. and Shungin, Dmitry and van Duijn, Cornelia M. and Tanaka, Toshiko and de Andrade, Mariza and Manning, Alisa K. and Hivert, Marie-France and Grimsby, Jonna L. and Liu, Ching-Ti and Bielak, Lawrence F. and Hottenga, Jouke-Jan and Jackson, Anne U. and Bouatia-Naji, Nabila and Lahti, Jari and Lecoeur, Cecile and de Faire, Ulf and Martínez-Larrad, María Teresa and Chen, Han and Navarro, Pau and Montasser, May E. and Perry, John R. B. and Rasmussen-Torvik, Laura J. and Rybin, Denis and An, Ping and Andrews, Jeanette S. and de Geus, Eco and Aspelund, Thor and Atalay, Mustafa and Aulchenko, Yurii and Balkau, Beverley and Johnson, Toby and Bandinelli, Stefania and Beckmann, Jacques S. and Prokopenko, Inga and Beilby, John P. and Ak, Manning and Bellis, Claire and Amin, Najaf and Diagram, Consortium and Bergman, Richard N. and Blangero, John and Boban, Mladen and Ingelsson, Erik and Barnes, Daniel and Boehnke, Michael and Boerwinkle, Eric and Mt, Martinez Larrad and Cadby, Gemma and Bonnycastle, Lori Ll and Mf, Hivert and Boomsma, Dorret I. and Liu, Ym and Borecki, Ingrid B. and Me, Montasser and Böttcher, Yvonne and Bouchard, Claude and Kanoni, Stavroula and Jr, Perry and Brunner, Eric and Lj, Rasmussen Torvik and Budimir, Danijela and Ladenvall, Claes and Campbell, Harry and Carlson, Olga and Liu, Yongmei and Chines, Peter S. and Lagou, Vasiliki and Clarke, Robert and Rj, Strawbridge and Collins, Francis S. and Cm, van Duijn and Js, Andrews and Couper, David and De Andrade, M. and Dedoussis, George V. and Corbatón-Anchuelo, Arturo and Deloukas, Panos and Ra, Scott and Dimitriou, Maria and Egan, Josephine M. and Jl, Grimsby and Eiriksdottir, Gudny and Erdos, Michael R. and Eriksson, Johan G. and Js, Beckmann and Räikkönen, Katri and Eury, Elodie and Ferrucci, Luigi and Jp, Beilby and Ford, Ian and Forouhi, Nita G. and Rn, Bergman and Fox, Caroline S. and Saaristo, Timo and Sabater-Lleal, Maria and Savage, David B. and Franzosi, Maria Grazia and Salomaa, Veikko and Ll, Bonnycastle and Franks, Paul W. and Saxena, Richa and Frayling, Timothy M. and Di, Boomsma and Schwarz, Peter and Froguel, Philippe and Shuldiner, Alan R. and Galan, Pilar and Ib, Borecki and Sijbrands, Eric J. G. and Seedorf, Udo and Siscovick, David S. and Sennblad, Bengt and Gigante, Bruna and Smit, Johannes H. and Serrano-Ríos, Manuel and Glazer, Nicole L. and Small, Kerrin S. and Boettcher, Yvonne and Goel, Anuj and Smith, Nicholas L. and Groop, Leif and Smith, Albert Vernon and Gudnason, Vilmundur and Ps, Chines and Hallmans, Göran and Stančáková, Alena and Hamsten, Anders and Sun, Yan V. and Stirrups, Kathleen and Hansson, Ola and Swift, Amy J. and Stumvoll, Michael and Fs, Collins and Tönjes, Anke and Harris, Tamara B. and Hayward, Caroline and Jj, Hottenga and Tuomilehto, Jaakko and Heath, Simon and Uitterlinden, Andre G. and Trompet, Stella and Hercberg, Serge and Gv, Dedoussis and Hicks, Andrew Aa and Uusitupa, Matti and De Faire, U. and Hingorani, Aroon and Vohl, Marie-Claude and Vikström, Max and Voight, Benjamin F. and Vitart, Veronique and Hofman, Albert and Jm, Egan and Mr, Erdos and Hui, Jennie and Vollenweider, Peter and Waterworth, Dawn M. and Hung, Joseph and Waeber, Gerard and Jarvelin, Marjo-Riitta and Watkins, Hugh and Au, Jackson and Jhun, Min A. and Wheeler, Eleanor and Johnson, Paul C. D. and Wild, Sarah H. and Widen, Elisabeth and Jukema, Jw Wouter and Ng, Forouhi and Willems, Sara M. and Jula, Antti and Kao, Wh H. and Wilson, James F. and Willemsen, Gonneke and Kaprio, Jaakko and Witteman, Jacqueline C. M. and Cs, Fox and Wright, Alan F. and Keinanen-Kiukaanniemi, Sirkka and Kardia, Sharon L. R. and Yaghootkar, Hanieh and Kivimaki, Mika and Mg, Franzosi and Zelenika, Diana and Kolcic, Ivana and Zemunik, Tatijana and Kovacs, Peter and Zgaga, Lina and Pw, Franks and Wareham, Nicholas J. and Kumari, Meena and Kuusisto, Johanna and Jg, Eriksson and Watanabe, Richard M. and Ct, Liu and Kyvik, Kirsten Ohm and Laakso, Markku and Lakka, Timo and De Geus, E. and Lannfelt, Lars and Nl, Glazer and Leander, Karin and Launer, Lenore J. and Li, Guo and Lf, Bielak and Lind, Lars and Lathrop, Gm Mark and Lindström, Jaana and Lobbens, Stéphane and Luan, Jian’an and Aa, Hicks and Loos, Ruth J. F. and Lyssenko, Valeriya and Mr, Jarvelin and Marmot, Michael and Mägi, Reedik and Ma, Jhun and Meneton, Pierre and Magnusson, Patrik K. E. and Mooser, Vincent and Pc, Johnson and Jw, Jukema and Miljkovic, Iva and Mohlke, Karen L. and Morken, Mario A. and Narisu, Narisu and O'Connell, Jeff and Ko, Kyvik and Ong, Ken Kk and Palotie, Aarno and Oostra, Ben A. and Gm, Lathrop and Palmer, Lyle J. and Lj, Launer and Pehlic, Marina and Pankow, James S. and Peltonen, Leena and Penninx, Brenda W. J. H. and Peden, John F. and Rj, Loos and Pericic, Marijana and Pk, Magnusson and Pedersen, Nancy L. and Perola, Markus and Perusse, Louis and Kl, Mohlke and Polasek, Ozren and Magi, Reedik and Rauramaa, Rainer and Ma, Morken and Pramstaller, Peter Pp and Peyser, Patricia A. and Kk, Ong and Province, Michael A. and Rehnberg, Emil and Ba, Oostra and Rice, Ken and Rotter, Jerome I. and Lj, Palmer and Rudan, Igor and Ruokonen, Aimo and Mark Lathrop, G. and Js, Pankow and Jf, Peden and Nl, Pedersen and Pa, Peyser and Pp, Pramstaller and Ma, Province and Ji, Rotter and Raikkonen, Katri and Db, Savage and Ar, Shuldiner and Ej, Sijbrands and Ds, Siscovick and Böttcher, Yvonne and Jh, Smit and Ks, Small and Nl, Smith and Av, Smith and Aj, Swift and Ag, Uitterlinden and Mc, Vohl and Bf, Voight and Dm, Waterworth and Jf, Wilson and Jc, Witteman and Af, Wright and Mr, Järvelin and Geus, E. J. C. and Consortium, DIAbetes Genetics Replication And Meta-Analysis (Diagram) and Mägi, Reedik and Consortium, Multiple Tissue Human Expression Resource (MUTHER) and O’Connell, Jeff and Nj, Wareham and Pérusse, Louis and Mi, McCarthy and McCarthy, Mark I. and Barroso, Inês and Rm, Watanabe and Florez, Jose C. and Jc, Florez and Dupuis, Josee and Meigs, James B. and Jb, Meigs and Langenberg, Claudia and , },
  doi = {10.1038/ng.2274},
  month = {jan},
  title = {A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance},
  url = {http://www.nature.com/articles/ng.2274.pdf},
  year = {2012}
}

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A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Journal article published in 2012 by Consortium Muther, J. Wouter Jukema, Robert A. Scott, Anke Tönjes, Cm M. Van Duijn, Frayling Tm, Harris Tb, Kao Wh, Kardia Sl, Sun Yv, Anke Toenjes, Wild Sh, Willems Sm, Perttu Salo, Naveed Sattar and other authors. Consortium Muther, J. Wouter Jukema, Robert A. Scott, Anke Tönjes, Cm M. Van Duijn, Frayling Tm, Harris Tb, Kao Wh, Kardia Sl, Sun Yv, Anke Toenjes, Wild Sh, Willems Sm, Perttu Salo, Naveed Sattar, Rona J. Strawbridge

, Dmitry Shungin, Cornelia M. van Duijn, Toshiko Tanaka, Mariza de Andrade, Alisa K. Manning, Marie-France Hivert, Jonna L. Grimsby, Ching-Ti Liu, Lawrence F. Bielak, Jouke-Jan Hottenga, Anne U. Jackson, Nabila Bouatia-Naji, Jari Lahti

, Cecile Lecoeur, Ulf de Faire, María Teresa Martínez-Larrad, Han Chen, Pau Navarro

, May E. Montasser, John R. B. Perry, Laura J. Rasmussen-Torvik

, Denis Rybin, Ping An, Jeanette S. Andrews, Eco de Geus, Thor Aspelund, Mustafa Atalay, Yurii Aulchenko, Beverley Balkau, Toby Johnson

, Stefania Bandinelli, Jacques S. Beckmann, Inga Prokopenko

, John P. Beilby, Manning Ak, Claire Bellis, Najaf Amin, Consortium Diagram, Richard N. Bergman, John Blangero, Mladen Boban, Erik Ingelsson, Daniel Barnes, Michael Boehnke, Eric Boerwinkle, Martinez Larrad Mt, Gemma Cadby, Lori Ll Bonnycastle, Hivert Mf, Dorret I. Boomsma, Ym Liu, Ingrid B. Borecki, Montasser Me, Yvonne Böttcher, Claude Bouchard, Stavroula Kanoni, Perry Jr, Eric Brunner, Rasmussen Torvik Lj, Danijela Budimir, Claes Ladenvall, Harry Campbell, Olga Carlson, Yongmei Liu, Peter S. Chines, Vasiliki Lagou, Robert Clarke, Strawbridge Rj, Francis S. Collins, van Duijn Cm, Andrews Js, David Couper, M. De Andrade, George V. Dedoussis, Arturo Corbatón-Anchuelo, Panos Deloukas

, Scott Ra, Maria Dimitriou, Josephine M. Egan, Grimsby Jl, Gudny Eiriksdottir, Michael R. Erdos, Johan G. Eriksson, Beckmann Js, Katri Räikkönen, Elodie Eury, Luigi Ferrucci, Beilby Jp, Ian Ford, Nita G. Forouhi, Bergman Rn, Caroline S. Fox, Timo Saaristo, Maria Sabater-Lleal, David B. Savage, Maria Grazia Franzosi, Veikko Salomaa, Bonnycastle Ll, Paul W. Franks, Richa Saxena, Timothy M. Frayling, Boomsma Di, Peter Schwarz, Philippe Froguel, Alan R. Shuldiner, Pilar Galan, Borecki Ib, Eric J. G. Sijbrands, Udo Seedorf

, David S. Siscovick, Bengt Sennblad, Bruna Gigante, Johannes H. Smit, Manuel Serrano-Ríos, Nicole L. Glazer, Kerrin S. Small, Yvonne Boettcher, Anuj Goel, Nicholas L. Smith, Leif Groop, Albert Vernon Smith

, Vilmundur Gudnason, Chines Ps, Göran Hallmans, Alena Stančáková, Anders Hamsten, Yan V. Sun, Kathleen Stirrups, Ola Hansson

, Amy J. Swift, Michael Stumvoll, Collins Fs, Anke Tönjes, Tamara B. Harris, Caroline Hayward, Hottenga Jj, Jaakko Tuomilehto, Simon Heath, Andre G. Uitterlinden, Stella Trompet, Serge Hercberg, Dedoussis Gv, Andrew Aa Hicks, Matti Uusitupa, U. De Faire, Aroon Hingorani, Marie-Claude Vohl, Max Vikström, Benjamin F. Voight, Veronique Vitart, Albert Hofman, Egan Jm, Erdos Mr, Jennie Hui, Peter Vollenweider, Dawn M. Waterworth, Joseph Hung, Gerard Waeber, Marjo-Riitta Jarvelin, Hugh Watkins, Jackson Au, Min A. Jhun, Eleanor Wheeler, Paul C. D. Johnson, Sarah H. Wild, Elisabeth Widen, Jw Wouter Jukema, Forouhi Ng, Sara M. Willems, Antti Jula, Wh H. Kao, James F. Wilson, Gonneke Willemsen, Jaakko Kaprio, Jacqueline C. M. Witteman, Fox Cs, Alan F. Wright, Sirkka Keinanen-Kiukaanniemi, Sharon L. R. Kardia, Hanieh Yaghootkar, Mika Kivimaki

, Franzosi Mg, Diana Zelenika, Ivana Kolcic, Tatijana Zemunik, Peter Kovacs, Lina Zgaga, Franks Pw, Nicholas J. Wareham, Meena Kumari, Johanna Kuusisto, Eriksson Jg, Richard M. Watanabe, Liu Ct, Kirsten Ohm Kyvik, Markku Laakso, Timo Lakka, E. De Geus, Lars Lannfelt, Glazer Nl, Karin Leander

, Lenore J. Launer, Guo Li, Bielak Lf, Lars Lind, Gm Mark Lathrop, Jaana Lindström, Stéphane Lobbens, Jian’an Luan, Hicks Aa, Ruth J. F. Loos, Valeriya Lyssenko, Jarvelin Mr, Michael Marmot, Reedik Mägi, Jhun Ma, Pierre Meneton, Patrik K. E. Magnusson, Vincent Mooser, Johnson Pc, Jukema Jw, Iva Miljkovic

, Karen L. Mohlke, Mario A. Morken, Narisu Narisu, Jeff O'Connell, Kyvik Ko, Ken Kk Ong, Aarno Palotie, Ben A. Oostra, Lathrop Gm, Lyle J. Palmer, Launer Lj, Marina Pehlic, James S. Pankow, Leena Peltonen, Brenda W. J. H. Penninx, John F. Peden, Loos Rj, Marijana Pericic, Magnusson Pk, Nancy L. Pedersen, Markus Perola, Louis Perusse, Mohlke Kl, Ozren Polasek, Reedik Magi, Rainer Rauramaa, Morken Ma, Peter Pp Pramstaller

, Patricia A. Peyser, Ong Kk, Michael A. Province, Emil Rehnberg, Oostra Ba, Ken Rice, Jerome I. Rotter, Palmer Lj, Igor Rudan, Aimo Ruokonen, G. Mark Lathrop, Pankow Js, Peden Jf, Pedersen Nl, Peyser Pa, Pramstaller Pp, Province Ma, Rotter Ji, Katri Raikkonen, Savage Db, Shuldiner Ar, Sijbrands Ej, Siscovick Ds, Yvonne Böttcher, Smit Jh, Small Ks, Smith Nl, Smith Av, Swift Aj, Uitterlinden Ag, Vohl Mc, Voight Bf, Waterworth Dm, Wilson Jf, Witteman Jc, Wright Af, Järvelin Mr, E. J. C. Geus, DIAbetes Genetics Replication And Meta-Analysis (Diagram) Consortium, Reedik Mägi, Multiple Tissue Human Expression Resource (MUTHER) Consortium, Jeff O’Connell, Wareham Nj, Louis Pérusse, McCarthy Mi, Mark I. McCarthy, Inês Barroso, Watanabe Rm, Jose C. Florez, Florez Jc, Josee Dupuis, James B. Meigs, Meigs Jb, Claudia Langenberg,

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Abstract

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

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A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Abstract