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

A.K. Manning, M.F. Hivert, R.A. Scott, J.L. Grimsby, N. Bouatia-Naji, H. Chen, D. Rybin, C.T. Liu, L.F. Bielak, I. Prokopenko, N. Amin, D. Barnes, G. Cadby, J.J. Hottenga, E. Ingelsson, D.I. Boomsma, E.J.C. de Geus, B.W.J.H. Penninx, G. Willemsen, J.F. WilsonJ.C.M. Witteman, A.F. Wright, H. Yaghootkar, D. Zelenika, T. Zemunik, L. Zgaga, N.J. Wareham, M.I. McCarthy, I. Barroso, R.M. Watanabe, J.C. Florez, J. Dupuis, J.B. Meigs, C. 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
Original languageEnglish
Pages (from-to)659-669
JournalNature Genetics
Volume44
Issue number6
DOIs
Publication statusPublished - 2012

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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. Nature Genetics, 44(6), 659-669. https://doi.org/10.1038/ng.2274