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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Manning, AK; Hivert, M-F; Scott, RA; Grimsby, JL; Bouatia-Naji, N; Chen, H; Rybin, D; Liu, C-T; Bielak, LF; Prokopenko, I; Amin, N; Barnes, D; Cadby, G; Hottenga, J-J; Ingelsson, E; Jackson, AU; Johnson, T; Kanoni, S; Ladenvall, C; Lagou, V; Lahti, J; Lecoeur, C; Liu, Y; Martinez-Larrad, MT; Montasser, ME; Navarro, P; Perry, JRB; Rasmussen-Torvik, LJ; Salo, P; Sattar, N; Shungin, D; Strawbridge, RJ; Tanaka, T; van Duijn, CM; An, P; de Andrade, M; Andrews, JS; Aspelund, T; Atalay, M; Aulchenko, Y; Balkau, B; Bandinelli, S; Beckmann, JS; Beilby, JP; Bellis, C; Bergman, RN; Blangero, J; Boban, M; Boehnke, M; Boerwinkle, E; Bonnycastle, LL; Boomsma, DI; Borecki, IB; Böttcher, Y; Bouchard, C; Brunner, E; Budimir, D; Campbell, H; Carlson, O; Chines, PS; Clarke, R; Collins, FS; Corbatón-Anchuelo, A; Couper, D; de Faire, U; Dedoussis, GV; Deloukas, P; Dimitriou, M; Egan, JM; Eiriksdottir, G; Erdos, MR; Eriksson, JG; Eury, E; Ferrucci, L; Ford, I; Forouhi, NG; Fox, CS; Franzosi, MG; Franks, PW; Frayling, TM; Froguel, P; Galan, P; de Geus, E; Gigante, B; Glazer, NL; Goel, A; Groop, L; Gudnason, V; Hallmans, G; Hamsten, A; Hansson, O; Harris, TB; Hayward, C; Heath, S; Hercberg, S; Hicks, AA; Hingorani, A; Hofman, A; Hui, J; Hung, J; Jarvelin, M-R; Jhun, MA; Johnson, PCD; Jukema, JW; Jula, A; Kao, WH; Kaprio, J; Kardia, SLR; Keinanen-Kiukaanniemi, S; Kivimaki, M; Kolcic, I; Kovacs, P; Kumari, M; Kuusisto, J; Kyvik, KO; Laakso, M; Lakka, T; Lannfelt, L; Lathrop, GM; Launer, LJ; Leander, K; Li, G; Lind, L; Lindstrom, J; Lobbens, S; Loos, RJF; Luan, J; Lyssenko, V; Mägi, R; Magnusson, PKE; Marmot, M; Meneton, P; Mohlke, KL; Mooser, V; Morken, MA; Miljkovic, I; Narisu, N; O'Connell, J; Ong, KK; Oostra, BA; Palmer, LJ; Palotie, A; Pankow, JS; Peden, JF; Pedersen, NL; Pehlic, M; Peltonen, L; Penninx, B; Pericic, M; Perola, M; Perusse, L; Peyser, PA; Polasek, O; Pramstaller, PP; Province, MA; Räikkönen, K; Rauramaa, R; Rehnberg, E; Rice, K; Rotter, JI; Rudan, I; Ruokonen, A; Saaristo, T; Sabater-Lleal, M; Salomaa, V; Savage, DB; Saxena, R; Schwarz, P; Seedorf, U; Sennblad, B; Serrano-Rios, M; Shuldiner, AR; Sijbrands, EJG; Siscovick, DS; Smit, JH; Small, KS; Smith, NL; Smith, AV; Stančáková, A; Stirrups, K; Stumvoll, M; Sun, YV; Swift, AJ; Tönjes, A; Tuomilehto, J; Trompet, S; Uitterlinden, AG; Uusitupa, M; Vikström, M; Vitart, V; Vohl, M-C; Voight, BF; Vollenweider, P; Waeber, G; Waterworth, DM; Watkins, H; Wheeler, E; Widen, E; Wild, SH; Willems, SM; Willemsen, G; Wilson, JF; Witteman, JCM; Wright, AF; Yaghootkar, H; Zelenika, D; Zemunik, T; Zgaga, L; DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, ; Multiple Tissue Human Expression Resource (MUTHER) Consortium, ; Wareham, NJ; McCarthy, MI; Barroso, I; Watanabe, RM; Florez, JC; Dupuis, J; Meigs, JB; Langenberg, C

Published Date

  • May 13, 2012

Published In

Volume / Issue

  • 44 / 6

Start / End Page

  • 659 - 669

PubMed ID

  • 22581228

Pubmed Central ID

  • 22581228

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/ng.2274

Language

  • eng

Conference Location

  • United States