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

Manning, A.K. et al. (2012) A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nature Genetics, 44, pp. 659-669. (doi:10.1038/ng.2274)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Johnson, Dr Paul and Ford, Professor Ian and Sattar, Professor Naveed and Strawbridge, Dr Rona
Authors: Manning, A.K., Hivert, M.-F., Scott, R.A., Grimsby, J.L., Bouatia-Naji, N., Chen, H., Rybin, D., Liu, C.-T., Bielak, L.F., Prokopenko, I., Amin, N., Barnes, D., Cadby, G., Hottenga, J.-J., Ingelsson, E., Jackson, A.U., Johnson, T., Kanoni, S., Ladenvall, C., Lagou, V., Lahti, J., Lecoeur, C., Liu, Y., Martinez-Larrad, M.T., Montasser, M.E., Navarro, P., Perry, J.R.B., Rasmussen-Torvik, L.J., Salo, P., Sattar, N., Shungin, D., Strawbridge, R.J., Tanaka, T., van Duijn, C.M., An, P., de Andrade, M., Andrews, J.S., Aspelund, T., Atalay, M., Aulchenko, Y., Balkau, B., Bandinelli, S., Beckmann, J.S., Beilby, J.P., Bellis, C., Bergman, R.N., Blangero, J., Boban, M., Boehnke, M., Boerwinkle, E., Bonnycastle, L.L., Boomsma, D.I., Borecki, I.B., Böttcher, Y., Bouchard, C., Brunner, E., Budimir, D., Campbell, H., Carlson, O., Chines, P.S., Clarke, R., Collins, F.S., Corbatón-Anchuelo, A., Couper, D., de Faire, U., Dedoussis, G.V., Deloukas, P., Dimitriou, M., Egan, J.M., Eiriksdottir, G., Erdos, M.R., Eriksson, J.G., Eury, E., Ferrucci, L., Ford, I., Forouhi, N.G., Fox, C.S., Franzosi, M.G., Franks, P.W., Frayling, T.M., Froguel, P., Galan, P., de Geus, E., Gigante, B., Glazer, N.L., Goel, A., Groop, L., Gudnason, V., Hallmans, G., Hamsten, A., Hansson, O., Harris, T.B., Hayward, C., Heath, S., Hercberg, S., Hicks, A.A., Hingorani, A., Hofman, A., Hui, J., Hung, J., Jarvelin, M.-R., Jhun, M.A., Johnson, P.C.D., Jukema, J.W., Jula, A., Kao, W.H., Kaprio, J., Kardia, S.L.R., Keinanen-Kiukaanniemi, S., Kivimaki, M., Kolcic, I., Kovacs, P., Kumari, M., Kuusisto, J., Kyvik, K.O., Laakso, M., Lakka, T., Lannfelt, L., Lathrop, G.M., Launer, L.J., Leander, K., Li, G., Lind, L., Lindstrom, J., Lobbens, S., Loos, R.J.F., Luan, J., Lyssenko, V., Mägi, R., Magnusson, P.K.E., Marmot, M., Meneton, P., Mohlke, K.L., Mooser, V., Morken, M.A., Miljkovic, I., Narisu, N., O'Connell, J., Ong, K.K., Oostra, B.A., Palmer, L.J., Palotie, A., Pankow, J.S., Peden, J.F., Pedersen, N.L., Pehlic, M., Peltonen, L., Penninx, B., Pericic, M., Perola, M., Perusse, L., Peyser, P.A., Polasek, O., Pramstaller, P.P., Province, M.A., Räikkönen, K., Rauramaa, R., Rehnberg, E., Rice, K., Rotter, J.I., Rudan, I., Ruokonen, A., Saaristo, T., Sabater-Lleal, M., Salomaa, V., Savage, D.B., Saxena, R., Schwarz, P., Seedorf, U., Sennblad, B., Serrano-Rios, M., Shuldiner, A.R., Sijbrands, E.J.G., Siscovick, D.S., Smit, J.H., Small, K.S., Smith, N.L., Smith, A.V., Stančáková, A., Stirrups, K., Stumvoll, M., Sun, Y.V., Swift, A.J., Tönjes, A., Tuomilehto, J., Trompet, S., Uitterlinden, A.G., Uusitupa, M., Vikström, M., Vitart, V., Vohl, M.-C., Voight, B.F., Vollenweider, P., Waeber, G., Waterworth, D.M., Watkins, H., Wheeler, E., Widen, E., Wild, S.H., Willems, S.M., Willemsen, G., Wilson, J.F., Witteman, J.C.M., Wright, A.F., Yaghootkar, H., Zelenika, D., Zemunik, T., Zgaga, L., Wareham, N.J., McCarthy, M.I., Barroso, I., Watanabe, R.M., Florez, J.C., Dupuis, J., Meigs, J.B., and Langenberg, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
Journal Name:Nature Genetics
ISSN:1061-4036
ISSN (Online):1546-1718
Published Online:13 May 2012

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