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

Publication ,  Journal Article
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 ...
Published in: Nat Genet
May 13, 2012

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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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

May 13, 2012

Volume

44

Issue

6

Start / End Page

659 / 669

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Insulin Resistance
  • Insulin
  • Humans
  • Genome-Wide Association Study
  • Diabetes Mellitus, Type 2
  • Developmental Biology
  • Cholesterol, HDL
  • Body Mass Index
  • Blood Glucose
 

Citation

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ICMJE
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Manning, A. K., Hivert, M.-F., Scott, R. A., Grimsby, J. L., Bouatia-Naji, N., Chen, H., … Langenberg, C. (2012). A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet, 44(6), 659–669. https://doi.org/10.1038/ng.2274
Manning, Alisa K., Marie-France Hivert, Robert A. Scott, Jonna L. Grimsby, Nabila Bouatia-Naji, Han Chen, Denis Rybin, et al. “A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.Nat Genet 44, no. 6 (May 13, 2012): 659–69. https://doi.org/10.1038/ng.2274.
Manning AK, Hivert M-F, Scott RA, Grimsby JL, Bouatia-Naji N, Chen H, et al. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet. 2012 May 13;44(6):659–69.
Manning, Alisa K., et al. “A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.Nat Genet, vol. 44, no. 6, May 2012, pp. 659–69. Pubmed, doi:10.1038/ng.2274.
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. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet. 2012 May 13;44(6):659–669.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

May 13, 2012

Volume

44

Issue

6

Start / End Page

659 / 669

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Insulin Resistance
  • Insulin
  • Humans
  • Genome-Wide Association Study
  • Diabetes Mellitus, Type 2
  • Developmental Biology
  • Cholesterol, HDL
  • Body Mass Index
  • Blood Glucose