Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

Scott, R.A. et al. (2013) Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nature Genetics, 44(9), pp. 991-1005. (doi:10.1038/ng.2385)

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Abstract

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

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: Scott, R.A., Lagou, V., Welch, R.P., Wheeler, E., Montasser, M.E., Luan, J., Mägi, R., Strawbridge, R.J., Rehnberg, E., Gustafsson, S., Kanoni, S., Rasmussen-Torvik, L.J., Yengo, L., Lecoeur, C., Shungin, D., Sanna, S., Sidore, C., Johnson, P.C.D., Jukema, J.W., Johnson, T., Mahajan, A., Verweij, N., Thorleifsson, G., Hottenga, J.-J., Shah, S., Smith, A.V., Sennblad, B., Gieger, C., Salo, P., Perola, M., Timpson, N.J., Evans, D.M., Pourcain, B.S., Wu, Y., Andrews, J.S., Hui, J., Bielak, L.F., Zhao, W., Horikoshi, M., Navarro, P., Isaacs, A., O'Connell, J.R., Stirrups, K., Vitart, V., Hayward, C., Esko, T., Mihailov, E., Fraser, R.M., Fall, T., Voight, B.F., Raychaudhuri, S., Chen, H., Lindgren, C.M., Morris, A.P., Rayner, N.W., Robertson, N., Rybin, D., Liu, C.-T., Beckmann, J.S., Willems, S.M., Chines, P.S., Jackson, A.U., Kang, H.M., Stringham, H.M., Song, K., Tanaka, T., Peden, J.F., Goel, A., Hicks, A.A., An, P., Müller-Nurasyid, M., Franco-Cereceda, A., Folkersen, L., Marullo, L., Jansen, H., Oldehinkel, A.J., Bruinenberg, M., Pankow, J.S., North, K.E., Forouhi, N.G., Loos, R.J.F., Edkins, S., Varga, T.V., Hallmans, G., Oksa, H., Antonella, M., Nagaraja, R., Trompet, S., Ford, I., Bakker, S.J.L., Kong, A., Kumari, M., Gigante, B., Herder, C., Munroe, P.B., Caulfield, M., Antti, J., Mangino, M., Small, K., Miljkovic, I., Liu, Y., Atalay, M., Kiess, W., James, A.L., Rivadeneira, F., Uitterlinden, A.G., Palmer, C.N.A., Doney, A.S.F., Willemsen, G., Smit, J.H., Campbell, S., Polasek, O., Bonnycastle, L.L., Hercberg, S., Dimitriou, M., Bolton, J.L., Fowkes, G.R., Kovacs, P., Lindström, J., Zemunik, T., Bandinelli, S., Wild, S.H., Basart, H.V., Rathmann, W., Grallert, H., Maerz, W., Kleber, M.E., Boehm, B.O., Peters, A., Pramstaller, P.P., Province, M.A., Borecki, I.B., Hastie, N.D., Rudan, I., Campbell, H., Watkins, H., Farrall, M., Stumvoll, M., Ferrucci, L., Waterworth, D.M., Bergman, R.N., Collins, F.S., Tuomilehto, J., Watanabe, R.M., de Geus, E.J.C., Penninx, B.W., Hofman, A., Oostra, B.A., Psaty, B.M., Vollenweider, P., Wilson, J.F., Wright, A.F., Hovingh, G.K., Metspalu, A., Uusitupa, M., Magnusson, P.K.E., Kyvik, K.O., Kaprio, J., Price, J.F., Dedoussis, G.V., Deloukas, P., Meneton, P., Lind, L., Boehnke, M., Shuldiner, A.R., van Duijn, C.M., Morris, A.D., Toenjes, A., Peyser, P.A., Beilby, J.P., Körner, A., Kuusisto, J., Laakso, M., Bornstein, S.R., Schwarz, P.E.H., Lakka, T.A., Rauramaa, R., Adair, L.S., Smith, G.D., Spector, T.D., Illig, T., de Faire, U., Hamsten, A., Gudnason, V., Kivimaki, M., Hingorani, A., Keinanen-Kiukaanniemi, S.M., Saaristo, T.E., Boomsma, D.I., Stefansson, K., van der Harst, P., Dupuis, J., Pedersen, N.L., Sattar, N., Harris, T.B., Cucca, F., Ripatti, S., Salomaa, V., Mohlke, K.L., Balkau, B., Froguel, P., Pouta, A., Jarvelin, M.-R., Wareham, N.J., Bouatia-Naji, N., McCarthy, M.I., Franks, P.W., Meigs, J.B., Teslovich, T.M., Florez, J.C., Langenberg, C., Ingelsson, E., Prokopenko, I., and Barroso, I.
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
Publisher:Nature Publishing Group
ISSN:1061-4036
Published Online:12 August 2012

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